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Karunadhas NS, Catherwood M, Stringfellow H, Arora R, McCluggage WG. "Early" Clear Cell Proliferations (Clear Cell Carcinoma in Situ) in Ovarian Endometriotic Cysts: Report of a Case Series With Recommendations for Terminology. Am J Surg Pathol 2025:00000478-990000000-00517. [PMID: 40326407 DOI: 10.1097/pas.0000000000002415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Clear cell carcinoma (CCC) is an uncommon malignancy accounting for ∼12% of ovarian carcinomas. Most cases arise from endometriosis, frequently an endometriotic cyst. We report a series of 6 cases where clear cell proliferations, morphologically, and immunophenotypically consistent with CCC, involve the epithelial lining of an endometriotic cyst without invasion into the surrounding stroma. The patients were aged 29 to 63 years (mean 45). In all cases, epithelial proliferations composed of cells with atypical nuclei, sometimes with a hobnail morphology, and clear or eosinophilic cytoplasm involved the epithelial lining of an ovarian endometriotic cyst. In areas, the proliferations comprised a monolayer, but in all cases, there was also significant epithelial stratification and multilayering, sometimes with a pseudopapillary architecture. There was no invasion of the atypical cells into the surrounding ovarian stroma. The proliferations were positive for Napsin A (6 of 6; 4 diffuse, 2 focal), racemase (5 of 5; 3 diffuse, 2 focal), hepatocyte nuclear factor 1-beta (5 of 5; all diffuse), oestrogen receptor (5 of 6; 2 diffuse, 3 focal), and PAX8 (3 of 3; all diffuse). p53 was wild-type in all 6 cases and WT1 and progesterone receptor were negative in the 4 and 6 cases tested, respectively. Mismatch repair immunohistochemistry was retained in the 3 cases tested. Next-generation sequencing was performed in 2 cases. In 1 case, a sole pathogenic MSH6 variant (p.Ser65fs) was identified. Follow-up (2 to 24 months) was available in 5 cases and there was no tumour recurrence. In reporting these "early" clear cell proliferations in endometriotic cysts, we provide recommendations for the reporting pathologist regarding the most appropriate terminology, which is important in patient management. We suggest that these proliferations be termed "CCC in situ" and that identification of such a lesion should prompt extensive sampling in order to exclude an invasive CCC component within the stroma outside the endometriotic cyst lining. We also stress the importance of close dialogue between the pathologist and the clinician and between the clinician and the patient in order to avoid overtreatment in such cases.
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Affiliation(s)
| | - Mark Catherwood
- Regional Molecular Diagnostics Service, Belfast Health and Social Care Trust, Belfast, Northern Ireland
| | | | - Rupali Arora
- Department of Cellular Pathology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
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de Santiago PR, Sato S, Zhang SJ, Dougher MC, Devins KM, Bilecz AJ, Rayamajhi S, Mingo G, Rendulich HS, Feng Y, Wu C, Taylor MS, Zhuravlev Y, Jung E, Omran DK, Wang TL, Shih IM, Schwartz LE, Kim S, Morgan MA, Tanyi JL, Burns KH, Lengyel E, Parra-Herran C, Godwin AK, Walt DR, Drapkin R. LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker. NPJ Precis Oncol 2025; 9:62. [PMID: 40050409 PMCID: PMC11885553 DOI: 10.1038/s41698-025-00849-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 02/24/2025] [Indexed: 03/09/2025] Open
Abstract
Long interspersed element 1 (LINE-1) retrotransposons are repetitive sequences that can move within the genome by an autonomous mechanism. To limit their mutagenic potential, benign cells restrict LINE-1 expression through molecular mechanisms such as DNA methylation and histone modification, but these mechanisms are usually impaired in cancer. Clear cell ovarian carcinoma (CCOC) represents 5-10% of ovarian cancers and is thought to arise from endometriosis. Women with advanced CCOC face poor prognoses, highlighting the importance of understanding early disease pathogenesis. In our study, 33 of 40 cases (over 82%) of CCOC tumors express ORF1p, a LINE-1-encoded protein. We found that LINE-1 de-repression is an early event in CCOC, as ORF1p is enhanced during the transition from typical to atypical endometriosis and persists in invasive cancer. Finally, using single-molecule array (Simoa) assays, we detected ORF1p in patient blood, suggesting it as a potential minimally invasive biomarker for this disease.
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Affiliation(s)
- Pamela R de Santiago
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Sho Sato
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Stephanie J Zhang
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA
| | - Meaghan C Dougher
- Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Kyle M Devins
- Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Agnes J Bilecz
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Sagar Rayamajhi
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Gabriel Mingo
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Hannah S Rendulich
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Yi Feng
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Connie Wu
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA
| | - Martin S Taylor
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Yelena Zhuravlev
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Euihye Jung
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Dalia K Omran
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Tian-Li Wang
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ie-Ming Shih
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lauren E Schwartz
- Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Sarah Kim
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Mark A Morgan
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Janos L Tanyi
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Kathleen H Burns
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Pathology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Ernst Lengyel
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL, USA
| | - Carlos Parra-Herran
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew K Godwin
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA
- Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - David R Walt
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA
| | - Ronny Drapkin
- Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
- Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
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Giannini A, Massimello F, Caretto M, Cosimi G, Mannella P, Luisi S, Gadducci A, Simoncini T. Factors in malignant transformation of ovarian endometriosis: A narrative review. Gynecol Endocrinol 2024; 40:2409911. [PMID: 39445672 DOI: 10.1080/09513590.2024.2409911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 06/12/2024] [Accepted: 09/19/2024] [Indexed: 10/25/2024] Open
Abstract
Endometriosis is a common estrogen-dependent inflammatory disease with a chronic course and a tendency to recur. The association between endometriosis and cancer has been studied for several years. Numerous reports have demonstrated a strong association between specific ovarian malignancies and endometriotic lesions. Atypical endometriosis has been widely described as a malignant precursor to ovarian epithelial tumors, particularly clear cell carcinomas and endometrioid carcinomas. These histological types associated with endometriosis develop predominantly in the ovary rather than in extragonadal sites. The detailed molecular mechanism of etiology remains unclear. Recent studies have analyzed the genetic and molecular mechanisms involved in endometriosis-associated ovarian cancer. A critical role appears to be played by a carcinogenic model based on iron-induced oxidative stress, which is typical of the endometriosis microenvironment. It has been hypothesized that trans-tubal reflux of blood, endometrial cells and associated iron-induced oxidative stress underlie the development of endometriosis-associated ovarian cancer. However, the multifactorial mechanisms of this malignant transformation are not fully understood. The aim of this review is to summaries the current epidemiological, histopathological, genetic and molecular findings in the progression of endometriosis-associated ovarian cancer.
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Affiliation(s)
- Andrea Giannini
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy
| | - Francesca Massimello
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy
| | - Marta Caretto
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy
| | - Giulia Cosimi
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy
| | - Paolo Mannella
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy
| | - Stefano Luisi
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy
| | - Angiolo Gadducci
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy
| | - Tommaso Simoncini
- Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy
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McMullan JC, Graham MJ, Craig EF, McCluggage WG, Hunter DH, Feeney L. The malignant transformation of endometriosis: Is there a left lateral predisposition of ovarian clear cell and endometrioid carcinomas? EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108247. [PMID: 38522332 DOI: 10.1016/j.ejso.2024.108247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/21/2024] [Accepted: 03/03/2024] [Indexed: 03/26/2024]
Abstract
INTRODUCTION Endometriosis affects 10% of women of reproductive age. There is evidence for a left lateral predisposition of endometriotic lesions and a 1.9-fold greater risk of ovarian cancer in endometriosis. The aim of this study is to determine whether a left lateral predisposition of ovarian clear-cell carcinoma (CCC) and endometrioid carcinoma (EC) exists. MATERIALS AND METHODS A retrospective cohort study of all EC and CCC patients in Northern Ireland between March-2011 and June-2018. ANOVA was used to analyse preoperative prediction of stage, chi-squared (χ2) was used to compare left- and right-sided masses. Survival was estimated using Kaplan-Meier and log-rank test. A p-value <0.05 was considered significant. RESULTS 158 patients were identified (95 EC, 55 CCC, 8 mixed). Mean age was 57.65 years with 69% presenting at stage 1. The mean CA125 was 559 U/mL (p = 0.850) and mean abdominal mass size was 14.12 cm (p = 0.732). The most common presenting symptom was an abdominal mass (37%). Despite 67% of patients having endometriosis on final pathology, only 8.9% had a known history pre-operatively. 51% of tumours were located on the left (p = 0.036). For unilateral tumours this was significant for EC (P = 0.002) but not for CCC (P = 0.555). The 1-, 3- and 5-year overall survival for all types/stages was 85%, 78% and 71% respectively. CONCLUSION While CCC and EC are associated with endometriosis, only EC exhibits a left lateral predisposition. There is no association between preoperative CA125 or abdominal mass size and stage of disease.
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Affiliation(s)
| | - Michael J Graham
- Department of Gynaecology, Belfast City Hospital, Belfast, NI, BT9 7AB, UK
| | - Elaine F Craig
- Department of Gynaecology, Belfast City Hospital, Belfast, NI, BT9 7AB, UK
| | - W Glenn McCluggage
- Department of Pathology, Belfast City Hospital, Belfast, NI, BT9 7AB, UK
| | - David H Hunter
- Department of Gynaecology, Belfast City Hospital, Belfast, NI, BT9 7AB, UK
| | - Laura Feeney
- Patrick G Johnson Centre for Cancer Research (PGJCCR), Queen's University Belfast, Belfast, NI, BY9 7AE, UK
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Pejovic T, Cathcart AM, Alwaqfi R, Brooks MN, Kelsall R, Nezhat FR. Genetic Links between Endometriosis and Endometriosis-Associated Ovarian Cancer-A Narrative Review (Endometriosis-Associated Cancer). Life (Basel) 2024; 14:704. [PMID: 38929687 PMCID: PMC11204815 DOI: 10.3390/life14060704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/15/2024] [Accepted: 05/23/2024] [Indexed: 06/28/2024] Open
Abstract
Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma-EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the PTEN tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC.
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Affiliation(s)
- Tanja Pejovic
- Department of Obstetrics and Gynecology, Providence Medical Center and Providence Cancer Institute, Medford, OR 97504, USA;
| | - Ann M. Cathcart
- Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97201, USA;
| | - Rofieda Alwaqfi
- Department of Pathology and Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; (R.A.); (F.R.N.)
| | - Marjorie N. Brooks
- Department of Obstetrics and Gynecology, Providence Medical Center and Providence Cancer Institute, Medford, OR 97504, USA;
| | - Rachel Kelsall
- Pacific Northwest University of Health Sciences, Yakima, WA 98901, USA;
| | - Farr R. Nezhat
- Department of Pathology and Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; (R.A.); (F.R.N.)
- Weill Cornell Medical College, Cornell University, New York, NY 10065, USA
- NYU Long Island School of Medicine, Mineola, NY 11501, USA
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Capozzi VA, Scarpelli E, dell’Omo S, Rolla M, Pezzani A, Morganelli G, Gaiano M, Ghi T, Berretta R. Atypical Endometriosis: A Comprehensive Systematic Review of Pathological Patterns and Diagnostic Challenges. Biomedicines 2024; 12:1209. [PMID: 38927416 PMCID: PMC11201022 DOI: 10.3390/biomedicines12061209] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/20/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024] Open
Abstract
Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance.
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Affiliation(s)
| | | | | | - Martino Rolla
- Department of Obstetrics and Gynecology, University Hospital of Parma, 43125 Parma, Italy
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Calmon MS, Lemos FFB, Silva Luz M, Rocha Pinheiro SL, de Oliveira Silva LG, Correa Santos GL, Rocha GR, Freire de Melo F. Immune pathway through endometriosis to ovarian cancer. World J Clin Oncol 2024; 15:496-522. [PMID: 38689629 PMCID: PMC11056862 DOI: 10.5306/wjco.v15.i4.496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/29/2024] [Accepted: 03/18/2024] [Indexed: 04/22/2024] Open
Abstract
Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer. Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer, representing an earlier stage of neoplastic processes. This is particularly true for women with clear cell carcinoma, low-grade serous carcinoma and endometrioid. However, the carcinogenic pathways between both pathologies remain poorly understood. Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers (EAOCs) via pathways associated with oxidative stress, inflammation, and hyperestrogenism. This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis, specifically focusing on the complex relationship between the immune response to endometriosis and cancer, including the molecular mechanisms and their ramifications. Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.
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Affiliation(s)
- Mariana Santos Calmon
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabian Fellipe Bueno Lemos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Samuel Luca Rocha Pinheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Gabriel Lima Correa Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Gabriel Reis Rocha
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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Chang YT, Lu TF, Sun L, Shih YH, Hsu ST, Liu CK, Hwang SF, Lu CH. Case report: Malignant transformation of ovarian endometrioma during long term use of dienogest in a young lady. Front Oncol 2024; 14:1338472. [PMID: 38357201 PMCID: PMC10864460 DOI: 10.3389/fonc.2024.1338472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 01/15/2024] [Indexed: 02/16/2024] Open
Abstract
Endometriosis is a benign disease, which is also regarded as a precursor to ovarian malignancy. Dienogest is a progestin treatment for endometriosis with efficacy and tolerability. A 35-year-old Taiwanese lady with ovarian endometrioma had taken dienogest for the last 5 years. During sonographic follow-up, surgery was suggested owing to suspicious of malignant transformation of ovarian endometrioma. While she hesitated and turned to receive two cycles of oocyte retrieval because of nulliparity. Meanwhile, more papillary growth in the ovarian endometrioma with intratumor flow was found during follow-up. Laparoscopic enucleation was performed later, and pathology revealed clear cell carcinoma with peritoneal involvement, at least FIGO stage IIB. She then underwent debulking surgery to grossly no residual tumor and received adjuvant chemotherapy with no tumor recurrence in post-operative 17-months follow-up. Considering fertility preservation, conservative treatment of ovarian endometrioma is typically indicated for those women who have not yet completed childbearing. However, malignant transformation may still occur despite long-term progestin treatment. Therefore, careful image follow-up is still indispensable.
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Affiliation(s)
- Yi-Ting Chang
- Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ting-Fang Lu
- Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Lou Sun
- Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Food and Nutrition, Providence University, Taichung, Taiwan
| | - Yu-Hsiang Shih
- Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan
- College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan
| | - Shih-Tien Hsu
- Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan
- Center for General Education, Ling Tung University, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Chin-Ku Liu
- Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan
| | - Sheau-Feng Hwang
- Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Palliative Care Unit, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chien-Hsing Lu
- Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung, Taiwan
- Institute of Biomedical Sciences, Ph.D. Program in Translational Medicine, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
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Ke X, Liang XF, Wang F. Management of a Nulliparous IVF Patient with a Declined Ovarian Reserve After Discovery of an Atypical Ovarian Endometriotic Cyst. Int J Womens Health 2023; 15:1475-1480. [PMID: 37810202 PMCID: PMC10557980 DOI: 10.2147/ijwh.s431837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 09/26/2023] [Indexed: 10/10/2023] Open
Abstract
Purpose Endometriosis (EM) is a common cause of infertility, and an ovarian endometriotic cyst may affect the ovarian reserve, ovulation, and endometrial receptivity. The majority of EM cases are benign; however, EM may also be prone to malignant transformation, associated with infiltrative growth, and recurrent or distant metastasis. In this study, we report the management of an atypical cyst discovered through ovarian endometriotic cyst puncture prior to controlled ovarian stimulation (COS). Case Presentation The patient required in vitro fertilization treatment due to EM and bilateral fallopian tube obstruction. Prior to initiating gonadotropin (Gn) treatment, the right ovarian EM cyst was punctured; cytological pathology of the obtained fluid revealed an atypical morphology. Subsequently, the case was discussed with the patient and ethically reviewed. Gn was initiated according to the patient's wishes, and six day-3 embryos were finally obtained and cryopreserved. Afterwards, laparoscopic cystectomy of the ovarian endometrioma revealed no malignant transformation. The patient achieved clinical pregnancy after resuscitation and transplantation of the embryo. Conclusion In summary, patients with EM-associated infertility are at risk of ovarian cancer formation when undergoing assisted reproduction treatment; therefore, this risk should be evaluated and minimized before initiating such treatment.
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Affiliation(s)
- Xue Ke
- Department of Reproductive Medicine, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Xue-Fei Liang
- Department of Reproductive Medicine, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
| | - Fang Wang
- Department of Reproductive Medicine, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China
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10
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Kobayashi H. Clinicopathological characteristics, molecular features and novel diagnostic strategies for the detection of malignant transformation of endometriosis (Review). Exp Ther Med 2023; 25:279. [PMID: 37206546 PMCID: PMC10189589 DOI: 10.3892/etm.2023.11978] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 01/20/2023] [Indexed: 05/21/2023] Open
Abstract
Endometriosis is a benign gynecological disease that affects women of reproductive age. Although malignant transformation of endometriosis is rare, physicians must be aware of this due to the high incidence of clear cell carcinoma of the ovary (CCC) in Japan. The most prevalent histological subtype of ovarian cancer is CCC (~70%) followed by endometrioid carcinoma (30%). The present review discusses the clinicopathological and molecular features of endometriosis-associated ovarian cancer (EAOC) as well as prospects for novel diagnostic strategies. Papers published between 2000 and 2022 in the PubMed and Google Scholar databases were included. Contents of the endometriotic cyst fluid may be involved in carcinogenesis, although the underlying mechanisms are largely unknown. Some studies have proposed a possible mechanism wherein excessive hemoglobin, heme and iron could cause an imbalance in intracellular redox homeostasis in endometriotic cells. Combined with DNA damage and mutations, the imbalances may induce the development of EAOC. Endometriotic cells evolve to adapt to the prolonged unfavorable oxidative microenvironmental stress. On the other hand, macrophages enhance the antioxidative defense mechanism and protect endometriotic cells against oxidative damage through intercellular crosstalk and signaling pathways. Therefore, changes in redox signaling, energy metabolism and the tumor immune microenvironment could be the key elements in the malignant transformation of certain endometriotic cell clones. Additionally, non-invasive bioimaging (i.e., magnetic resonance relaxometry) and biomarkers (i.e., tissue factor pathway inhibitor 2) may be promising tools for early-stage detection of the disease. In conclusion, the present review summarizes the latest advancements in research on the biological characteristics and early diagnosis of malignant transformation of endometriosis.
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Affiliation(s)
- Hiroshi Kobayashi
- Department of Gynecology, Ms.Clinic MayOne, Kashihara, Nara 634-0813, Japan
- Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634-8522, Japan
- Correspondence to: Dr Hiroshi Kobayashi, Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan
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11
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Younis JS. Endometriosis-Associated Ovarian Cancer: What Are the Implications for Women with Intact Endometrioma Planning for a Future Pregnancy? A Reproductive Clinical Outlook. Biomolecules 2022; 12:1721. [PMID: 36421735 PMCID: PMC9688199 DOI: 10.3390/biom12111721] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/14/2022] [Accepted: 11/18/2022] [Indexed: 08/16/2023] Open
Abstract
Endometriosis is a chronic, universal, and prevalent disease estimated to affect up to 1:10 women of reproductive age. Endometriosis-associated ovarian cancer (EAOC) developing at reproductive age is challenging and of concern for women and practitioners alike. This outlook review focuses on the occurrence of EAOC, especially in infertile women or those planning for a future pregnancy, from the perspective of a reproductive endocrinologist, based on recent evidence. Contemporary pathogenesis, genetic profiles, evidence of causality, clinical diagnosis, prognosis, and up-to-date management are discussed. EAOC seems to be merely associated with endometrioma and includes clear-cell and endometrioid ovarian carcinoma. Although endometrioma is frequently found in women of reproductive age (up to 1:18 of women), EAOC appears to be a rare occurrence. These women are of more advanced reproductive age, nulliparous, and hyperestrogenic, with a large-sized unilateral endometrioma (>9 cm) containing solid components and papillary projections. Each case suspected to have EAOC has specific characteristics, and a multidisciplinary discussion and appropriate patient counseling should be conducted to reach an optimal therapeutic plan. Since most of these cases are diagnosed at an early stage with a favorable prognosis, fertility-sparing surgery may be feasible. The pros and cons of fertility preservation techniques should be discussed.
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Affiliation(s)
- Johnny S. Younis
- Reproductive Medicine, Department of Obstetrics and Gynecology, Baruch-Padeh Medical Center, Poriya 15208, Israel; ; Tel.: +972-505286981; Fax: +972-46737478
- Azrieli Faculty of Medicine in Galilee, Bar-Ilan University, Safed 1311502, Israel
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12
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Kim JM, Hong DG. Is ovarian cystectomy for atypical ovarian endometrioma safe?: A single center study. Medicine (Baltimore) 2022; 101:e30105. [PMID: 36107548 PMCID: PMC9439743 DOI: 10.1097/md.0000000000030272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Ovarian atypical endometriosis (AE) is a premalignant lesion, and its potential to progress to endometriosis-associated ovarian cancer emphasizes its significance. However, the true risk of malignancy in AE remains unclear. Therefore, this study aimed to investigate the clinical outcomes of ovarian AE after ovarian cystectomy. We retrospectively reviewed the medical records and histopathological reports of 41 patients who had been diagnosed with ovarian AE between January 2011 and April 2020. We reviewed age, obstetric history, age at menarche, preoperative CA 125 level, C-reactive protein level, erythrocyte sedimentation rate, endometriosis stage, mean follow-up duration, postoperative hormonal therapy, and prognosis, including recurrence of endometriosis and malignant transformation. Among 41 patients with pathologically diagnosed ovarian AE, 26 were followed up after cystectomy only. The average follow-up period was 58.27 ± 33.22 months in cystectomy only patients. The mean age of the patients with cystectomy only versus that of patients with endometriosis-associated ovarian carcinoma was 32.73 ± 6.10 versus 48.29 ± 4.35 (P < .01) years. The preoperative CA 125 level was 115.63 ± 219.06 versus 225.75 ± 163.39 (P < .051) U/mL. Patients with endometriosis-associated ovarian carcinoma or other diseases and those who underwent oophorectomy were excluded. After surgery, hormone therapy was administered to 22 of 26 patients, and the remaining 4 patients were followed up without additional treatment. Endometriosis recurrence occurred in 5 patients, 1 of whom underwent second-line laparoscopic ovarian cystectomy. However, no malignant transformations were observed. Ovarian AE has a low possibility of malignant transformation. Conservative treatment is recommended after appropriate ovarian cystectomy, such as enucleation.
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Affiliation(s)
- Jong Mi Kim
- Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- Department of Obstetrics and Gynecology, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea
| | - Dae Gy Hong
- Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
- Department of Obstetrics and Gynecology, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea
- *Correspondence: Dae Gy Hong, Department of Obstetrics and Gynecology, Kyungpook National University Chilgok Hospital, 807, Hoguk-ro, Buk-gu, Daegu 41404, Republic of Korea (e-mail: )
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13
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KRAS Mutation in Endometriosis-Associated Ovarian Borderline and Malignant Epithelial Tumors. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2022. [DOI: 10.5812/ijcm-120754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Endometriosis is a common disease among women with the capacity to transform into ovarian neoplasms. KRAS mutation is a keystone in tumor-genesis of many malignant neoplasms. Objectives: In the current study, we investigated KRAS mutations in endometriosis-associated ovarian borderline and malignant epithelial tumors. Methods: The specimens of 42 consecutive patients undergoing a surgical procedure whose final diagnosis comprised endometriosis-associated borderline and malignant epithelial ovarian tumors including 12 borderline epithelial tumors and 30 ovarian epithelial carcinomas were histopathologically reviewed. All cases were evaluated regarding the type of tumor, differentiation and simultaneous presence of endometriosis or atypical endometriosis. DNA extraction from the selected paraffin block was done and mutation of codons 12 and 13 was assessed. Results: Due to the quality of genomic DNA for PCR study was not acceptable in 6 out of 42 cases, among remaining 36 cases, KRAS mutation was observed in 6 cases including 2 cases with mutations in 2nd base of 12th codon (G→T), 3 cases with substitution of G→A in the 2nd base of 12th codon, and one with substitution of G→T in the 1st base of 12th codon. Conclusions: We evaluated the KRAS mutation in the spectrum of ovarian epithelial tumors associated with endometriosis for treatment approaches including targeted therapies. Our results suggested a possible link between KRAS mutation and endometriosis-associated ovarian borderline and malignant tumors but there was no convincing evidence to prove a definite linkage.
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14
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Vetvicka V, Fiala L, Garzon S, Buzzaccarini G, Terzic M, Laganà AS. Endometriosis and gynaecological cancers: molecular insights behind a complex machinery. PRZEGLAD MENOPAUZALNY = MENOPAUSE REVIEW 2021; 20:201-206. [PMID: 35069072 PMCID: PMC8764963 DOI: 10.5114/pm.2021.111276] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 08/28/2021] [Indexed: 12/11/2022]
Abstract
Endometriosis is described as the presence of both endometrial glandular and stromal cells outside the uterine cavity. A major characterization of this disease is ectopic implantation of endometrial cells with increased migration. It is one of the leading causes of morbidity among premenopausal women, with a prevalence of 10-16% of women of reproductive age. Despite over century of intensive research, none of the current treatment options represents a real cure. Based on the current knowledge, endometriosis, particularly its atypical version, is considered to be a transitional form from benign disease to tumour. However, the exact mechanisms of this conversion are still not fully established.
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Affiliation(s)
- Vaclav Vetvicka
- Department of Pathology, University of Louisville, Louisville, KY, United States
| | - Ludek Fiala
- Institute of Sexology, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Simone Garzon
- Department of Obstetrics and Gynecology, AOUI Verona, University of Verona, Verona, Italy
| | | | - Milan Terzic
- Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan
- Clinical Academic Department of Women's Health, National Research Center of Mother and Child Health, University Medical Center, Nur-Sultan, Kazakhstan
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Antonio Simone Laganà
- Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Varese, Italy
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15
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Sun Y, Liu G. Endometriosis-associated Ovarian Clear Cell Carcinoma: A Special Entity? J Cancer 2021; 12:6773-6786. [PMID: 34659566 PMCID: PMC8518018 DOI: 10.7150/jca.61107] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 09/12/2021] [Indexed: 02/06/2023] Open
Abstract
Endometriosis is an estrogen-dependent disease, which serves as a precursor of ovarian cancer, especially clear cell carcinoma (OCCC) and endometrial carcinoma. Although micro-environmental factors such as oxidative stress, immune cell dysfunction, inflammation, steroid hormones, and stem cells required for malignant transformation have been found in endometriosis, the exact carcinogenic mechanism remains unclear. Recent research suggest that many putative driver genes and aberrant pathways including ARID1A mutations, PIK3CA mutations, MET activation, HNF-1β activation, and miRNAs dysfunction, play crucial roles in the malignant transformation of endometriosis to OCCC. The clinical features of OCCC are different from other histological types. Patients usually present with a large, unilateral pelvic mass, and occasionally have thromboembolic vascular complications. OCCC patients are easier to be resistant to chemotherapy, have a worse prognosis, and are usually difficult to treat. To improve the survival of OCCC patients, it is necessary to better understand its specific carcinogenic mechanism and explore new treatment strategy, including molecular target.
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Affiliation(s)
- Yue Sun
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, China.,Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin, 300052, China
| | - Guoyan Liu
- Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, China.,Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin, 300052, China
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16
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So KA, Hong SR, Kim NR, Yang EJ, Shim SH, Lee SJ, Kim TJ. Association between atypical endometriosis and ovarian malignancies in the real world. J Ovarian Res 2021; 14:110. [PMID: 34454550 PMCID: PMC8403438 DOI: 10.1186/s13048-021-00865-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 05/30/2021] [Indexed: 11/18/2022] Open
Abstract
Background To evaluate the clinical outcome of atypical endometriosis and its association with ovarian malignancy. Methods This retrospective study included patients diagnosed with atypical endometriosis between January 2001 and December 2017. All patients had received surgical treatment for ovarian tumor. The clinical characteristics and histopathological results of all patients were reviewed. Results Atypical endometriosis was diagnosed in 101 patients. We analyzed 98 patients with a mean age of 34.8 years (range: 16–58 years). Ten patients (10.2%) had previously undergone endometriosis surgery more than once. In total, 12 (12.2%) patients had atypical endometriosis-associated ovarian malignancy—nine had carcinomas and three had borderline tumor. The tumors were pathologically classified as follows: five, clear cell carcinomas; two, endometrioid adenocarcinomas; one, mixed clear cell and endometrioid adenocarcinoma; one, seromucinous carcinoma; two, mucinous borderline tumors; and one, seromucinous borderline tumor. Conclusion Atypical endometriosis is most frequently associated with clear cell carcinoma and endometrioid adenocarcinoma. To identify the risk of ovarian malignancy and manage patients with endometriosis, diagnosing atypical endometriosis and recognizing its precancerous potential are important.
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Affiliation(s)
- Kyeong A So
- Department, of Obstetrics and Gynecology, Konkuk University School of Medicine, 120-1, Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea.,Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Seoul, Republic of Korea
| | - Sung Ran Hong
- Department of Pathology, CHA Ilsan Medical Center, CHA University, Gyeonggi-do, Republic of Korea.,Department of Pathology, Cheil General Hospital & Women's Healthcare Center, Seoul, Republic of Korea
| | - Nae Ri Kim
- Department, of Obstetrics and Gynecology, Konkuk University School of Medicine, 120-1, Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea
| | - Eun Jung Yang
- Department, of Obstetrics and Gynecology, Konkuk University School of Medicine, 120-1, Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea
| | - Seung-Hyuk Shim
- Department, of Obstetrics and Gynecology, Konkuk University School of Medicine, 120-1, Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea
| | - Sun Joo Lee
- Department, of Obstetrics and Gynecology, Konkuk University School of Medicine, 120-1, Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea
| | - Tae Jin Kim
- Department, of Obstetrics and Gynecology, Konkuk University School of Medicine, 120-1, Neungdong-ro, Gwangjin-gu, Seoul, 05030, Republic of Korea. .,Department of Obstetrics and Gynecology, Cheil General Hospital & Women's Healthcare Center, Seoul, Republic of Korea.
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17
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Abstract
Endometriosis will affect about 10% of the female population and not only can it significantly impact adversely on quality of life and result in infertility, but data are accumulating that malignant transformation is an important consideration. Endometriosis can be histologically typical or atypical, ovarian, superficial peritoneal or deep infiltrating. The precursor for malignant transformation appears to be the ovarian atypical endometriosis component. Ovarian cancer is the most important associated cancer, primarily endometrioid and clear cell cancer. These are the only subtypes wherein a direct clonal relationship between endometriosis, as a direct precursor, and cancer has been made. There is no substantive evidence to support an altered association of borderline cancers of the ovary, serous ovarian cancers and breast, endometrial or cervical cancers. This review provides an overview of the prevailing data pertaining to the molecular and genetic aberrations that accompany the transformation of atypical endometriosis to malignancy and the accumulated epidemiologic evidence which supports the association.
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Affiliation(s)
- F Guidozzi
- Parklane Clinic, Johannesburg, South Africa.,University of the Witwatersrand, Johannesburg, South Africa
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18
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Penciu RC, Postolache I, Steriu L, Izvoranu S, Tica AA, Mocanu ID, Sârbu V, Deacu M, Tica I, Bălţătescu GI, Tica OS, Tica VI. Is there a relationship in-between ovarian endometriosis and ovarian cancer? Immunohistochemical profile of four cases with coexisting ovarian endometriosis and cancer. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY 2021; 61:157-165. [PMID: 32747907 PMCID: PMC7728120 DOI: 10.47162/rjme.61.1.18] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Endometriosis (EMs) is a benign disease characterized by the presence of endometrial tissue outside the uterine cavity. EMs associated with ovarian cancer (OC) has a relative low incidence (5% to 10%), sometimes with evidence of a transition stage through atypical EMs (1.6% cases). We have assessed 135 consecutive patients with either EMs or OC and, out of them, our study reports on four cases of ovarian EMs and OC: two cases with endometrioid OC and two cases with high-grade serous OC (HGSOC). Cases with EMs and HGSOC are extremely rarely reported in the literature – we could find not more than 30 cases. The main objective of our research was to observe the possible similarities between EMs and OC. Secondly, we analyzed the differences between EMs associated with endometrioid OC and EMs associated with HGSOC. We evaluated them in terms of clinical status (age, stages of EMs and OC) and immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), Ki67, p53, p16, Wilms’ tumor 1 (WT1), cluster of differentiation (CD) 34 and CD10 immunomarkers – we could not find in the literature all these markers assessed, in the same time, to such samples. Our results indicated that there are no similarities between EMs and OC and no atypical EMs was identified in our cases. We recorded higher values of ER expression in EMs associated with HGSOC than in EMs associated with endometrioid OC. Higher values of ER expression were also recorded in OC than in endometriotic foci. There were no differences in proliferative rate of endometriotic foci associated with endometrioid OC, compared to EMs associated with HGSOC. An aberrant IHC expression for p53 protein and p16 protein was noted only in HGSOC. Also, a positive immunostaining for Wilms’ tumor 1 (WT1) was identified only in HGSOC. Higher values of microvessel density were recorded in OC but not in endometriotic foci. We concluded that there were no similarities between EMs and OC for the cases included in our study, but we noticed differences in terms of Ki67 index and also between hormonal receptors expression in EMs associated with HGSOC, comparing with EMs associated with endometrioid OCs. These results may represent a “brick” for future researches on the less understood EMs associated with type II of OCs, especially with HGSOC. Identifying the best marker, which can predict the risk of developing OC for the patients with EMs, may lead to discover new specific therapeutic agents and, therefore, a better, tailored, therapy.
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Sorbi F, Capezzuoli T, Saso S, Fambrini M, Corda M, Fantappiè G, Petraglia F. The relation between endometrioma and ovarian cancer. Minerva Obstet Gynecol 2021; 73:347-353. [PMID: 34008389 DOI: 10.23736/s2724-606x.21.04757-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
INTRODUCTION The relationship between endometrioma and ovarian cancer is a topic of discussion in the field of endometriosis and to date it is still debated whether ovarian endometriosis may represent a risk factor for ovarian cancers. EVIDENCE ACQUISITION A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to October 2020. Primary outcome of interest was ovarian cancer incidence in patients with endometriosis. Secondary outcome was ovarian cancer prognosis in patients with endometriosis compared to patient without endometriosis. EVIDENCE SYNTHESIS Patients with ovarian endometriosis has a slight increase risk of developing ovarian cancer (merely 1.8%), being the general population risk for ovarian cancer 1.31%. In patient at postmenopausal age, long-lasting endometriosis, early-age diagnosis, infertility and/or infertility treatment the risk of developing ovarian cancer is higher. Endometriosis-related ovarian cancers are generally clear cell and endometrioid and are diagnosed at early stage compared to non-endometriosis related ovarian cancer. CONCLUSIONS The lifetime risk for ovarian cancer is low in endometriosis patients in general and higher in subgroups of patients allowing a tailored management based on patient characteristics. Endometriosis is a chronic disease negatively affecting the quality of life, nonetheless, concerns on ovarian cancer should be avoided in order to reduce the burden of the disease on women's health.
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Affiliation(s)
- Flavia Sorbi
- Division of Obstetrics and Gynecology, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy -
| | - Tommaso Capezzuoli
- Division of Obstetrics and Gynecology, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Srdjan Saso
- Department of Gynecologic Oncology, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, UK
- Division of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Massimiliano Fambrini
- Division of Obstetrics and Gynecology, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Martina Corda
- Division of Obstetrics and Gynecology, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Giulia Fantappiè
- Division Obstetrics and Gynecology, Department of Maternity and Infancy, Careggi University Hospital, Florence, Italy
| | - Felice Petraglia
- Division of Obstetrics and Gynecology, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
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20
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Clinical and Pathological Significance of Cellular Atypia in Endometriosis. ACTA ACUST UNITED AC 2021; 57:medicina57050453. [PMID: 34066945 PMCID: PMC8148576 DOI: 10.3390/medicina57050453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Revised: 04/23/2021] [Accepted: 04/29/2021] [Indexed: 11/18/2022]
Abstract
Objective: To highlight the most frequent localization of ovarian endometriosis, the presence of atypical endometriosis, and recurrences. Retrospective review of 259 patients diagnosed with ovarian endometriosis treated at Tîrgu-Mures Emergency County Hospital, Obstetric Gynecology Clinic, between January 2014 and December 2018. Methods: Data were collected and analyzed for demographics, size of ovarian endometriotic cyst, and recurrences. Results: Out of 259 patients, 51 patients presented atypia, 20 on the right, 24 on the left, and seven patients were diagnosed with endometriosis with bilateral atypia. Higher susceptibility for left localization was noted. Thirty-nine patients (15.1%) presented recurrence. A statistically significant correlation (p = 0.006) was noted between patients with recurrence and atypia compared with those without atypia and endometriotic cysts larger than 7 cm. Patients with relapse under the age of 40 were noted to have mainly atypia with localization on the right (p = 0.025, OD = 4.107). Conclusions: The presence of endometrioma was not statistically significant correlated with left or right sided localization; recurrent endometriomas larger than 7 cm represents a risk for atypical endometriosis development. Recurrence and atypia appear more often in patients under the age of 40 and are right-sided. The total removal of the endometriomas can prevent the recurrence and subsequently the appearance of atypia and secondary neoplastic conditions.
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21
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Ponandai-Srinivasan S, Saare M, Boggavarapu NR, Frisendahl C, Ehrström S, Riethmüller C, García-Uribe PA, Rettkowski J, Iyengar A, Salumets A, Lalitkumar PGL, Götte M, Gemzell-Danielsson K. Syndecan-1 modulates the invasive potential of endometrioma via TGF-β signalling in a subgroup of women with endometriosis. Hum Reprod 2021; 35:2280-2293. [PMID: 32897364 DOI: 10.1093/humrep/deaa164] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 05/19/2020] [Indexed: 12/19/2022] Open
Abstract
STUDY QUESTION What is the physiological role of transforming growth factor-beta (TGF-β1) and syndecans (SDC1, SDC4) in endometriotic cells in women with endometriosis? SUMMARY ANSWER We observed an abnormal, pro-invasive phenotype in a subgroup of samples with ovarian endometriosis, which was reversed by combining gene silencing of SDC1 with the TGF-β1 treatment. WHAT IS KNOWN ALREADY Women with endometriosis express high levels of TGF-β1 and the proteoglycan co-receptors SDC1 and SDC4 within endometriotic cysts. However, how SDC1 and SDC4 expression is regulated by TGF-β1 and the physiological significance of the high expression in endometriotic cysts remains unknown as does the potential role in disease severity. STUDY DESIGN, SIZE, DURATION We utilized a pre-validated panel of stem- and cancer cell-associated markers on endometriotic tissue (n = 15) to stratify subgroups of women with endometriosis. Furthermore, CD90+CD73+CD105+ (SC+) endometriotic stromal cells from these patient subgroups were explored for their invasive behaviour in vitro by transient gene inhibition of SDC1 or SDC4, both in the presence or absence of TGF-β1 treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS Endometriotic cyst biopsies (n = 15) were obtained from women diagnosed with ovarian endometriosis (ASRM Stage III-IV). Gene expression variability was assessed on tissue samples by applying gene clustering tools for the dataset generated from the pre-validated panel of markers. Three-dimensional (3D) spheroids from endometriotic SC+ were treated in vitro with increasing doses of TGF-β1 or the TGFBRI/II inhibitor Ly2109761 and assessed for SDC1, SDC4 expression and in vitro 3D-spheroid invasion. Transcriptomic signatures from the invaded 3D spheroids were evaluated upon combining transient gene silencing of SDC1 or SDC4, both in presence or absence of TGF-β1 treatment. Furthermore, nanoscale changes on the surface of endometriotic cells were analysed after treatment with TGF-β1 or TGFBRI/II inhibitor using atomic force microscopy. MAIN RESULTS AND THE ROLE OF CHANCE Gene clustering analysis revealed that endometriotic tissues displayed variability in their gene expression patterns; a small subgroup of samples (2/15, Endo-hi) exhibited high levels of SDC1, SDC4 and molecules involved in TGF-β signalling (TGF-β1, ESR1, CTNNB1, SNAI1, BMI1). The remaining endometriotic samples (Endo-lo) showed a uniform, low gene expression profile. Three-dimensional spheroids derived from Endo-hi SC+ but not Endo-lo SC+ samples showed an aberrant expression of SDC1 and exhibited enhanced 3D-spheroid invasion in vitro, upon rhTGF-β1 treatment. However, this abnormal, pro-invasive response of Endo-hi SC+ was reversed upon gene silencing of SDC1 with the TGF-β1 treatment. Interestingly, transcriptomic signatures of 3D spheroids silenced for SDC1 and consecutively treated with TGF-β1, showed a down-regulation of cancer-associated pathways such as WNT and GPCR signalling. LARGE SCALE DATA Transcriptomic data were deposited in NCBI's Gene Expression Omnibus (GEO) and could be retrieved using GEO series accession number: GSE135122. LIMITATIONS, REASONS FOR CAUTION It is estimated that about 2.5% of endometriosis patients have a potential risk for developing ovarian cancer later in life. It is possible that the pro-oncogenic molecular changes observed in this cohort of endometriotic samples may not correlate with clinical occurrence of ovarian cancer later in life, thus a validation will be required. WIDER IMPLICATIONS OF THE FINDINGS This study emphasizes the importance of interactions between syndecans and TGF-β1 in the pathophysiology of endometriosis. We believe that this knowledge could be important in order to better understand endometriosis-associated complications such as ovarian cancer or infertility. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Cancerfonden (CAN 2016/696), Radiumhemmets Forskningsfonder (Project no. 154143 and 184033), EU MSCA-RISE-2015 project MOMENDO (691058), Estonian Ministry of Education and Research (IUT34-16), Enterprise Estonia (EU48695) and Karolinska Institute. Authors do not have any conflict of interest.
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Affiliation(s)
- Sakthivignesh Ponandai-Srinivasan
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden
| | - Merli Saare
- Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, 51014 Tartu, Estonia.,Competence Centre on Health Technologies, 50411 Tartu, Estonia
| | - Nageswara Rao Boggavarapu
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden
| | - Caroline Frisendahl
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden
| | - Sophia Ehrström
- Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, 171 77 Stockholm, Sweden.,UltraGyn Clinic, Sophiahemmet, Stockholm, Sweden
| | - Christoph Riethmüller
- Laboratory at Nanoanalytics in the Center for Nanotechnology, Serend-ip GmbH, CenTech, 48149 Münster, Germany
| | - Pablo Angel García-Uribe
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden
| | - Jasmin Rettkowski
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden
| | - Aditi Iyengar
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden
| | - Andres Salumets
- Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, 51014 Tartu, Estonia.,Competence Centre on Health Technologies, 50411 Tartu, Estonia.,Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, 00290 Helsinki, Finland.,Institute of Genomics, University of Tartu, 51010 Tartu, Estonia
| | - Parameswaran Grace Luther Lalitkumar
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden
| | - Martin Götte
- Department of Gynecology and Obstetrics, Muenster University, Medical Center, D-48149 Muenster, Germany
| | - Kristina Gemzell-Danielsson
- Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, S-171 76 Stockholm, Sweden
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22
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Králíčková M, Vetvicka V, Laganà AS. Endometrial cancer-is our knowledge changing? Transl Cancer Res 2020; 9:7734-7745. [PMID: 35117376 PMCID: PMC8798081 DOI: 10.21037/tcr-20-1720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 04/29/2020] [Indexed: 11/27/2022]
Abstract
In developed countries, endometrial cancer (EC) is the most frequent gynecologic malignancy in postmenopausal women. At the same time, EC has become one of the most common cancers in numerous developing countries, probably influenced by global epidemic of obesity. The majority of patients have low-grade endometrioid cancer with a high 5-year survival rate, but with high-risk EC, the survival rates are still rather low. However, despite intensive research in last decades, our knowledge of the mechanisms, risk factors, diagnosis and treatment have not significantly improved. The standard treatment of all types of EC is still a traditional combination of surgery, irradiation and/or chemotherapy, despite the fact that each of these options is not without having some negative side effects. Despite the fact that on the molecular level, EC is relatively well-studied, but the efforts to transform these findings into either diagnosis or therapies of EC remain elusive. In addition, some research into risk factors involved in the development or progression of EC seems to be more a fishing expedition than a well thought-out approach. The purpose of this review is to summarize the most recent developments in the search for biomarkers and prognostic markers and to discuss the progress in EC treatment.
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Affiliation(s)
- Milena Králíčková
- Department of Histology and Embryology, Faculty of Medicine, Charles University, Karlovarska 48, Plzen, Czech Republic.,Department of Obstetrics and Gynecology, University Hospital, Faculty of Medicine, Charles University, Alej Svobody 80, Plzen, Czech Republic.,Biomedical Centre, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic
| | - Vaclav Vetvicka
- Department of Pathology, University of Louisville, Louisville, KY, USA
| | - Antonio Simone Laganà
- Department of Obstetrics and Gynecology, "Filippo Del Ponte" Hospital, University of Insubria, Piazza Biroldi 1, Varese, Italy
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23
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Yachida N, Yoshihara K, Suda K, Nakaoka H, Ueda H, Sugino K, Yamaguchi M, Mori Y, Yamawaki K, Tamura R, Ishiguro T, Isobe M, Motoyama T, Inoue I, Enomoto T. ARID1A protein expression is retained in ovarian endometriosis with ARID1A loss-of-function mutations: implication for the two-hit hypothesis. Sci Rep 2020; 10:14260. [PMID: 32868822 PMCID: PMC7459315 DOI: 10.1038/s41598-020-71273-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 08/10/2020] [Indexed: 12/22/2022] Open
Abstract
ARID1A loss-of-function mutation accompanied by a loss of ARID1A protein expression is considered one of the most important driver events in endometriosis-associated ovarian cancer. Although our recent genomic study clarified that ARID1A loss-of-function mutations were detected in 13% of ovarian endometriosis, an association between the ARID1A mutation status and ARID1A protein expression in ovarian endometriosis remains unclear. We performed immunohistochemical staining for ARID1A in 78 ovarian endometriosis samples and 99 clear cell carcinoma samples. We revealed that not only 70 endometriosis samples without ARID1A mutations but also eight endometriosis samples with ARID1A loss-of-function mutations retained ARID1A protein expression. On the other hand, most of clear cell carcinomas with ARID1A loss-of-function mutations showed a loss of ARID1A protein expression. In particular, clear cell carcinoma samples which harbor multiple ARID1A loss-of-function mutations or both a single ARID1A loss-of-function mutation and ARID1A allelic imbalance lost ARID1A protein expression. However, ARID1A protein expression was retained in seven clear cell carcinomas with ARID1A loss-of-function mutations. These results suggest that a single ARID1A loss-of-function mutation is insufficient for ARID1A loss in ovarian endometriosis and some clear cell carcinoma. Further driver events may be needed for the malignant transformation of ovarian endometriosis with ARID1A loss-of-function mutations.
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Affiliation(s)
- Nozomi Yachida
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Kosuke Yoshihara
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan.
| | - Kazuaki Suda
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Hirofumi Nakaoka
- Human Genetics Laboratory, National Institute of Genetics, Mishima, 411-8540, Japan.,Department of Cancer Genome Research, Sasaki Institute, Sasaki Foundation, Chiyoda-ku, Tokyo, 101-0062, Japan
| | - Haruka Ueda
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Kentaro Sugino
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Manako Yamaguchi
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Yutaro Mori
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Kaoru Yamawaki
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Ryo Tamura
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Tatsuya Ishiguro
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Masanori Isobe
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
| | - Teiichi Motoyama
- Department of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan
| | - Ituro Inoue
- Human Genetics Laboratory, National Institute of Genetics, Mishima, 411-8540, Japan
| | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ward, Niigata, 951-8510, Japan
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24
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McCluggage WG. Endometriosis-related pathology: a discussion of selected uncommon benign, premalignant and malignant lesions. Histopathology 2020; 76:76-92. [PMID: 31846535 DOI: 10.1111/his.13970] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Endometriosis is an extremely common condition and, in most cases, establishing a histological diagnosis is straightforward, although a variety of benign alterations may result in problems with interpretation. In this review, I discuss selected uncommon variants of endometriosis or benign alterations that may result in diagnostic problems. The topics covered include the contentious issue of so-called atypical endometriosis, stromal endometriosis, polypoid endometriosis, and the association of endometriosis with florid mesothelial hyperplasia. The propensity of endometriosis to undergo neoplastic transformation (especially to endometrioid and clear cell carcinoma) is well known. Selected issues relating to the various neoplasms that can arise in endometriosis are discussed, with a particular concentration on unusual variants of endometrioid carcinoma that result in a disproportionately high number of issues in referral practice. The propensity of ovarian endometrioid carcinomas to show an unexpected ('aberrant') immunophenotype with positive staining with 'intestinal' markers and negative staining with Mullerian markers is also discussed. Uncommon tumour types that may arise in endometriosis, namely seromucinous neoplasms, mesonephric-like carcinomas, and somatically derived yolk sac tumours, are also covered.
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Affiliation(s)
- W Glenn McCluggage
- Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK
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25
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Santoro A, Angelico G, Inzani F, Spadola S, Arciuolo D, Valente M, Fiorentino V, Mulè A, Scambia G, Zannoni GF. The Many Faces of Endometriosis-Related Neoplasms in the Same Patient: A Brief Report. Gynecol Obstet Invest 2020; 85:371-376. [PMID: 32570258 DOI: 10.1159/000508225] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 04/27/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Endometriosis is a common benign gynecological condition that can be associated with a slightly increased risk of developing a wide range of malignancies. CASE PRESENTATION We herein report a singular case of a 62-year-old woman with a history of pelvic endometriosis, referred to our institution for chronic pelvic pain and uterine bleeding, with clinical and radiological evidence of left ovarian mass of 18 cm in largest diameter and multiple nodular mural lesions of the uterine cavity. The patient underwent exploratory laparotomy followed by hysterectomy, bilateral salpingo-oophorectomy, and omentectomy with pelvic lymph-node sampling. The histological examination of the ovarian mass revealed a clear-cell ovarian carcinoma arising from an endometriotic cyst. The microscopic examination of the uterine cavity showed multiple conventional leiomyomas, diffuse foci of adenomyosis, and a 1.5-cm yellow nodule diagnosed as low-grade endometrial stromal sarcoma associated with glandular atypical differentiation and with extension into parametrial and omental tissues. Following the diagnosis, the patient was treated with chemotherapy, radiation therapy, and hormonal therapy and after 9 months of follow-up is alive without local recurrences and distant metastases. DISCUSSION/CONCLUSIONS To the best of our knowledge, the present case represents the first evidence of the simultaneous occurrence of clear-cell carcinoma and low-grade endometrial stromal sarcoma arising within ovarian and uterine endometriotic foci, respectively.
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Affiliation(s)
- Angela Santoro
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giuseppe Angelico
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Frediano Inzani
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Saveria Spadola
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Damiano Arciuolo
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Michele Valente
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Vincenzo Fiorentino
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonino Mulè
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Giovanni Scambia
- Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Unità di Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.,Istituto di Clinica Ostetrica e Ginecologica, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Gian Franco Zannoni
- Unità di Gineco-Patologia e Patologia Mammaria, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, .,Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Rome, Italy,
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26
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Abstract
BACKGROUND Endometriosis is complex, but identifying the novel biomarkers, inflammatory molecules, and genetic links holds the key to the enhanced detection, prediction and treatment of both endometriosis and endometriosis related malignant neoplasia. Here we review the literature relating to the specific molecular mechanism(s) mediating tumorigenesis arising within endometriosis. METHODS Guidance (e.g. Cochrane) and published studies were identified. The Published studies were identified through PubMed using the systematic review methods filter, and the authors' topic knowledge. These data were reviewed to identify key and relevant articles to create a comprehensive review article to explore the molecular fingerprint associated with in endometriosis-driven tumorigenesis. RESULTS An important focus is the link between C3aR1, PGR, ER1, SOX-17 and other relevant gene expression profiles and endometriosis-driven tumorigenesis. Further studies should also focus on the combined use of CA-125 with HE-4, and the role for OVA1/MIA as clinically relevant diagnostic biomarkers in the prediction of endometriosis-driven tumorigenesis. CONCLUSIONS Elucidating endometriosis' molecular fingerprint is to understand the molecular mechanisms that drive the endometriosis-associated malignant phenotype. A better understanding of the predictive roles of these genes and the value of the biomarker proteins will allow for the derivation of unique molecular treatment algorithms to better serve our patients.
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27
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Comparative immunohistochemical study of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis including description of a perineural invasion. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020; 165:69-79. [PMID: 32158015 DOI: 10.5507/bp.2020.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 02/14/2020] [Indexed: 01/19/2023] Open
Abstract
AIM Endometriosis is an inflammatory condition that shares a number of similarities with malignant diseases, such as an abnormal morphology, migration along the nerve bundles and metastatic spread to lymph nodes and distant organs. Endometriotic lesions are associated with oestrogen and progesterone imbalance which seems to play a key role in the pathogenesis of endometriosis. The aim of this study was to compare the status of both oestrogen and progesterone receptors in tissue of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis using immunohistochemical methods, as well as to investigate the relationship between endometriosis and protein p53. METHODS A total of 40 cases with deep infiltrating endometriosis were included in our study. Based on histopathological analysis of resected specimens, the cases were divided into 2 groups: group 1 - lymph node endometriosis (cases with lymph node involvement; n=12) and group 2 - deep infiltrating endometriosis (cases without lymph node involvement; n=28). As a control group, eutopic endometrium of adenomyosis- and endometriosis-free women were used (n=16). Five cases of atypical ovarian endometriosis as well as descriptions of the nerve involvement in endometriosis were also included. Immunohistochemical staining with a total of 4 markers was performed - oestrogen and progesterone receptors (ER, PR), p53 and Ki-67 (proliferation index). RESULTS The immunophenotype of the cases in groups 1 and 2 and in the control group was virtually identical in the proliferative phase - strong nuclear ER and PR expression in more than 90% of endometrial glandular and stromal cells. In the early and mid secretory phase, ER expression only slightly decreased (80%) in endometrial glandular cells in group 2 and the control group, whereas in the late secretory phase, significant decrease of ER expression only in the control group was observed (15-50%; P<0.001). In group 2 and the control group, significant decrease of PR expression only in endometrial glandular cells was observed in the mid and late secretory phase (less than 15%; P<0.001). Differences in receptor content were found only in isolated cases in group 2. In group 1, no secretory changes were found. In all three groups, sporadic and weak nuclear p53 expression in less than 3% in both endometrial glandular and stromal cells was detected (regardless of the phase of the menstrual cycle). In atypical ovarian endometriosis, higher and strong p53 expression (on average 26%) and decrease in ER (on average 56%) and PR (less than 1%) expression was observed; compared to the control group and groups 1 and 2, the differences for all 3 markers were highly significant (P<0.001). In all groups, the proliferation index (Ki-67) reached the highest values in the proliferation phase and decreased during the cycle. However, in endometriotic tissue, it was widely variable in the individual phases of the cycle. Perineural spread of endometriosis with significant neural hypertrophy, hyperplasia and involvement of the ganglia of the autonomic nervous system was detected in 5 cases (12.5%). Conlusion. From a histological and immunohistochemical point of view, deep infiltrating endometriosis and lymph node endometriosis appear to represent the same entity. For the first time, a simple immunohistochemical panel with antibodies against ER, PR and p53 useful in diagnosing atypical endometriosis has been described. The marked endometriosis-associated neural changes (endometriotic neuropathy) could be one of the causes of impaired function of the affected organs after debulking surgery with macroscopic negative resection margins as well as pain symptomatology in macroscopic inapparent endometriotic lesions.
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28
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Ng SW, Norwitz SG, Taylor HS, Norwitz ER. Endometriosis: The Role of Iron Overload and Ferroptosis. Reprod Sci 2020; 27:1383-1390. [PMID: 32077077 DOI: 10.1007/s43032-020-00164-z] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 11/26/2019] [Indexed: 02/08/2023]
Abstract
Iron is an essential element for cell survival, and iron deficiency is a known risk factor for many reproductive disorders. Paradoxically, such disorders are also seen more commonly under conditions of iron excess. Here, we focus on the problem of iron overload in women's health, using endometriosis as a model system. We propose (i) that a primary defect in endometriosis is abnormal eutopic endometrium characterized by resistance to ferroptosis, a process of iron-mediated non-apoptotic programmed cell death, which allows cells spread via retrograde menstruation to survive, implant, and establish endometriotic lesions within the abdominal cavity, and (ii) that dysregulated iron homeostasis may be critical to the subsequent pathophysiology of endometriotic lesions with localized iron overload and inflammation. We further investigate the association between endometriosis and hypercholesterolemia and suggest that an interaction between the mevalonate cholesterol biosynthetic pathway and ferroptosis signaling may provide a molecular basis to explain how it is that, in some women, endometrial tissues survive and thrive under ferroptotic pressure, colonize at ectopic sites, and expand into endometriotic lesions.
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Affiliation(s)
- Shu-Wing Ng
- Department of Obstetrics & Gynecology, Tufts University School of Medicine, Boston, USA.,Mother Infant Research Institute, Tufts Medical Center, Boston, USA
| | | | - Hugh S Taylor
- Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, USA
| | - Errol R Norwitz
- Department of Obstetrics & Gynecology, Tufts University School of Medicine, Boston, USA. .,Mother Infant Research Institute, Tufts Medical Center, Boston, USA.
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29
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Cheng H, Wang Z, Cui L, Wen Y, Chen X, Gong F, Yi H. Opportunities and Challenges of the Human Microbiome in Ovarian Cancer. Front Oncol 2020; 10:163. [PMID: 32133297 PMCID: PMC7040031 DOI: 10.3389/fonc.2020.00163] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 01/29/2020] [Indexed: 12/13/2022] Open
Abstract
Ovarian cancer is the most lethal malignancy among gynecological cancers worldwide. Most ovarian cancer patients are diagnosed at an advanced stage because of non-specific clinical symptoms. The human microbiome plays a crucial role in maintaining the normal physiological and pathological state of the body. With the development of technologies such as DNA and 16S rRNA sequencing, an increasing number of findings on the role of microbiome in cancers are being reported. Microbiome abnormalities are increasingly associated with diseases, including cancer development, and response to therapies. Some studies have shown the relationship between microbiome changes and ovarian cancer. However, the mechanisms underlying this relationship are not yet fully understood. Here, we summarize the key findings in this regard by focusing on estrogen metabolism and host recognition receptors in microorganisms and changes in the gut or pelvic microbiome in patients with ovarian cancer. We further discuss the potential of using the microbiome as a novel biomarker for cancers. We also highlight the possibility to use microorganisms as a treatment modality to enhance the immune system, activate anti-tumor response, mediate chemotherapy resistance, and ameliorate the adverse effects of the treatment.
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Affiliation(s)
- Huiyan Cheng
- Department of Gynecology and Obstetrics, The First Hospital of Jilin University, Changchun, China
| | - Zhichao Wang
- Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, China
| | - Lifeng Cui
- Department of Gynecology and Obstetrics, The First Hospital of Jilin University, Changchun, China
| | - Yan Wen
- Department of Gynecology and Obstetrics, The First Hospital of Jilin University, Changchun, China
| | - Xiuhua Chen
- Department of Gynecology and Obstetrics, The First Hospital of Jilin University, Changchun, China
| | - Fengyan Gong
- Department of Gynecology and Obstetrics, The First Hospital of Jilin University, Changchun, China
| | - Huanfa Yi
- Central Laboratory of the Eastern Division, The First Hospital of Jilin University, Changchun, China
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30
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Abstract
Peri/postmenopausal endometriosis is not as rare as once we thought. Accumulated data revealed that around 1/3-1/4 of women with surgically-diagnosed endometriosis after the age of 40. The uneasiness of the issue of malignant transformation or malignancy in such women created a challenge for us. Here the management strategy for women with endometriosis after the age of 40 is discussed in the light of scientific evidence.
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Affiliation(s)
- Engin Oral
- Private practitioner, Istanbul, Turkey -
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31
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Abstract
This review is an appraisal of the current state of knowledge of 2 enigmatic histotypes of ovarian carcinoma: endometrioid and clear cell carcinoma. Both show an association endometriosis and the hereditary nonpolyposis colorectal cancer (Lynch) syndrome, and both typically present at an early stage. Pathologic and immunohistochemical features that distinguish these tumors from high-grade serous carcinomas, each other, and other potential mimics are discussed, as are staging, grading, and molecular pathogenesis.
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Affiliation(s)
- Oluwole Fadare
- Department of Pathology, University of California San Diego, San Diego, CA, USA.
| | - Vinita Parkash
- Department of Pathology, Yale School of Medicine, 20 York Street, EP2-607, New Haven, CT 06510, USA
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32
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Králíčková M, Laganà AS, Ghezzi F, Vetvicka V. Endometriosis and risk of ovarian cancer: what do we know? Arch Gynecol Obstet 2019; 301:1-10. [DOI: 10.1007/s00404-019-05358-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 10/25/2019] [Indexed: 12/15/2022]
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33
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Zhang Y, Qu P. Factors associated with ovarian endometriosis malignancy and its recurrence in Chinese women. J OBSTET GYNAECOL 2019; 39:1148-1153. [PMID: 31307261 DOI: 10.1080/01443615.2019.1603209] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
In this study, the risk factors for ovarian endometriosis (OE) malignancy and its recurrence were explored in Chinese women. For OE malignancy occurrence, the age of marriage, abortion times, course of OE, body mass index (BMI), other benign uterine complications, and shorter parturition times were identified as risk factors using univariate analyses. Among them, age at marriage, course of OE, BMI, and decreased parturition times were identified as risk factors using multivariate analyses. For OE malignancy recurrence, the risk factors included clinical staging, histological classification, and chemotherapy by univariate analysis; and clinical stage, clear-cell carcinoma, and fewer chemotherapy cycles by multivariate analyses. In summary, we concluded that higher ages at marriage, longer courses of ovarian endometriosis, shorter parturition times, and additional benign uterine complications may increase the risk of OE malignancy. Advanced clinical stages, clear-cell carcinomas, and fewer chemotherapy cycles may promote OE malignancy recurrence. Impact statement What is already known on this subject? Endometriosis is one of the most common gynaecological diseases. Although endometriosis is not a malignant disease, endometriosis cells have characteristics similar to cancer cells. The risk of malignant transformation rates of ovarian endometriosis is said to be 1:18. However, epidemiological evidence based on large population research in ovarian endometriosis malignancy is lacking. In addition, there were few studies focussing on the long-term prognosis of ovarian endometriosis malignancies. What do the results of this study add? This study revealed the possible occurrence and recurrence risk factors of ovarian endometriosis malignancy using univariate and multivariate statistics analyses. What are the implications of these findings for clinical practice and/or further research? A clinical retrospective study with a longer follow-up period is suggested for assessing the occurrence and recurrence risk factors for ovarian endometriosis malignancies.
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Affiliation(s)
- Ying Zhang
- Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics , Tianjin , China
| | - Pengpeng Qu
- Department of Gynecologic Oncology, Tianjin Central Hospital of Gynecology Obstetrics , Tianjin , China
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34
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Jiao Y, Lu B. Poorly differentiated mucinous carcinoma with signet ring cells in an ovarian endometriotic cyst: a case report. Diagn Pathol 2019; 14:73. [PMID: 31279332 PMCID: PMC6612217 DOI: 10.1186/s13000-019-0850-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 06/25/2019] [Indexed: 01/14/2023] Open
Abstract
Background Ovarian signet ring cell carcinomas are predominantly metastatic. Cases coexisting with endometriotic cysts are extremely rare, and are supposed to be primary. However, such cases have not been well-documented to date. Case presentation A 46-year-old Chinese woman had an incidental small nodule in the right ovarian endometriotic cyst. She underwent a staging surgery due to an unexpected ovarian carcinoma from her frozen section. Laparotomy exploration, MRI and gastrointestinal endoscopy revealed no other abnormalities in the abdominal organs. She had a pelvic recurrence at 7 months and was alive with disease for 13 months at present. Gross examination showed a small mural nodule (l.0 × 0.5 × 0.2 cm) in the wall of the right ovarian cyst (18x15x14 cm). Microscopically, the neoplastic cells arranged in solid nests, crowded small irregular glands and scattered single cells. They had abundant cytoplasmic mucin and contained a significant component of signet ring cells. The stroma was desmoplastic and occasionally contained extracellular mucin deposits. The surrounding endometriotic cyst had several foci of atypical surface epithelium (atypical endometriotic cyst) that was continuous with the mucinous carcinoma. Immunohistochemistry demonstrated that the tumor cells were diffusely positive for CK7 and negative for CK20 and CDX2. Conclusions Primary ovarian poorly differentiated mucinous carcinoma with signet ring cells can occur in an atypical endometriotic cyst. This rare case addresses the necessity of careful and extensive pathological examination on large ovarian endometriotic cysts.
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Affiliation(s)
- Yurong Jiao
- Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Bingjian Lu
- Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China. .,Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
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Cheng H, Wang Z, Fu L, Xu T. Macrophage Polarization in the Development and Progression of Ovarian Cancers: An Overview. Front Oncol 2019; 9:421. [PMID: 31192126 PMCID: PMC6540821 DOI: 10.3389/fonc.2019.00421] [Citation(s) in RCA: 174] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 05/03/2019] [Indexed: 12/15/2022] Open
Abstract
Ovarian cancer is the most lethal gynecological malignancy worldwide. Most patients are diagnosed at late stages because of atypical symptoms and the lack of effective early diagnostic measures. The mechanisms underlying the oncogenesis and development of ovarian cancer are not clear. Macrophages, immune cells derived from the innate immune system, have two states of polarization (M1 and M2) that develop in response to different stimuli. The polarization and differentiation of macrophages into the cancer-inhibiting M1 and cancer-promoting M2 types represent the two states of macrophages in the tumor microenvironment. The interaction of polarized macrophages with cancer cells plays a crucial role in a variety of cancers. However, the effects of macrophage M1/M2 polarization on ovarian cancer have not yet been systematically and fully discussed. In this review, we discuss not only the occurrence, development and influences of macrophage polarization but also the association between macrophage polarization and ovarian cancer. The polarization of macrophages into the M1 and M2 phenotypes plays a pivotal role in ovarian cancer initiation, progression, and metastasis, and provides targets for macrophage-centered treatment in the cancer microenvironment for ovarian cancer therapy. We also addressed the regulation of macrophage polarization in ovarian cancer via noncoding RNAs, exosomes, and epigenetics.
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Affiliation(s)
- Huiyan Cheng
- Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, China.,Department of Gynecology and Obstetrics, The First Hospital of Jilin University, Changchun, China
| | - Zhichao Wang
- Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, China
| | - Li Fu
- Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, China
| | - Tianmin Xu
- Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, China
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Ñiguez Sevilla I, Machado Linde F, Marín Sánchez MDP, Arense JJ, Torroba A, Nieto Díaz A, Sánchez Ferrer ML. Prognostic importance of atypical endometriosis with architectural hyperplasia versus cytologic atypia in endometriosis-associated ovarian cancer. J Gynecol Oncol 2019; 30:e63. [PMID: 31074246 PMCID: PMC6543102 DOI: 10.3802/jgo.2019.30.e63] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 12/29/2018] [Accepted: 02/04/2019] [Indexed: 12/23/2022] Open
Abstract
Objective Patients with endometriosis are at increased risk of ovarian cancer. It has been suggested that atypical endometriosis is a precursor lesion of endometriosis-associated ovarian cancer (EAOC). The aim of this study is to evaluate if cytologic (cellular) atypia and architectural atypia (hyperplasia), histologic findings described as atypical endometriosis, play a different role in patients with EAOC. Methods A prospective study was conducted between January 2014 and April 2017 at our institution with patients undergoing surgery with a histologic diagnosis of endometriosis, ovarian cancer, or EAOC. The prevalence and immunohistologic study (Ki-67, BAF250a, COX-2) of cases of cellular and architectural atypia in endometriosis were analyzed. Results Two hundred and sixty-six patients were included: the diagnosis was endometriosis alone in 159 cases, ovarian cancer in 81, and EAOC in 26. Atypical endometriosis was reported in 23 cases (12.43%), 39.13% of them found in patients with EAOC. Endometriosis with cellular atypia was found mainly in patients without neoplasm (71.4%), and endometriosis with architectural atypia was seen in patients with ovarian cancer (88.9%) (p=0.009). Ki-67 was significantly higher in endometriosis patients with architectural atypia than those with cellular atypia. Conclusion The diagnosis of endometriosis with architectural atypia is important because it may be a precursor lesion of ovarian cancer; therefore, pathologists finding endometriosis should carefully examine the surgical specimen to identify any patients with hyperplasia-type endometriosis, as they may be at higher risk of developing EAOC.
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Affiliation(s)
- Isabel Ñiguez Sevilla
- Department of Obstetrics and Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, Murcia, Spain
| | | | | | - Julián Jesús Arense
- Preventive Medicine and Public Health, Department of Public Health Sciences, University of Murcia School of Medicine, Murcia, Spain
| | - Amparo Torroba
- Department of Pathology, 'Virgen de la Arrixaca' University Clinical Hospital, Murcia, Spain
| | - Anibal Nieto Díaz
- Department of Obstetrics and Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, Murcia, Spain
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Kajiyama H, Suzuki S, Yoshihara M, Tamauchi S, Yoshikawa N, Niimi K, Shibata K, Kikkawa F. Endometriosis and cancer. Free Radic Biol Med 2019; 133:186-192. [PMID: 30562557 DOI: 10.1016/j.freeradbiomed.2018.12.015] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 12/13/2018] [Accepted: 12/14/2018] [Indexed: 12/21/2022]
Abstract
Endometriosis, characterized by the presence of extra-uterine endometrium, is a common gynecologic disorder in reproductive-age women. Although the detailed molecular mechanism of etiology remains unelucidated, recent studies have gradually revealed both genetic and epigenetic backgrounds of the development of endometriosis. In clinical practice, endometriosis has been recognized as a precursor lesion of several types of malignancies and endometriosis-associated carcinoma. An imbalance between reactive oxygen species and local antioxidants has been reported to contribute to the development of endometriosis-associated carcinoma as well as the pathophysiology of this disease through a systemic inflammatory response in the peritoneal cavity. This review mainly presents an epidemiology, possible etiology of endometriosis, precursor lesions, molecular features, and the association between the microenvironmental accumulations of oxidative stress in endometriosis-associated ovarian cancer progression.
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Affiliation(s)
- Hiroaki Kajiyama
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Japan.
| | - Shiro Suzuki
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Japan
| | - Masato Yoshihara
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Japan
| | - Satoshi Tamauchi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Japan
| | - Nobuhisa Yoshikawa
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Japan
| | - Kaoru Niimi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Japan
| | - Kiyosumi Shibata
- Department of Obstetrics and Gynecology, Bantane Hospital, Fujita Health University, Japan
| | - Fumitaka Kikkawa
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Japan
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38
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Tanase Y, Kawaguchi R, Uchiyama T, Kobayashi H. Long-Term Follow-Up after Surgical Management for Atypical Endometriosis: A Series of Nine Cases. Case Rep Oncol 2019; 12:76-83. [PMID: 30792646 PMCID: PMC6381887 DOI: 10.1159/000496178] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Accepted: 12/06/2018] [Indexed: 11/20/2022] Open
Abstract
Background and Objective Atypical endometriosis is reported to possess a precancerous potential attributed to premalignant changes characterized by cytological atypia and architecture proliferation. Although the coexistence of atypical endometriosis and neoplasms has been reported, cases of atypical endometriosis transformation to carcinoma are rarely reported. The purpose of this case series was to evaluate the prognosis of atypical endometriosis. Subjects and Methods Data from nine women who underwent surgical treatment including cystectomy and salpingo-oophorectomy with or without hysterectomy and diagnosed with atypical endometriosis was analyzed. Between January 2006 and January 2018, the clinical characteristics and prognosis of atypical endometriosis were evaluated. Results During the follow-up period, eight of nine patients with atypical endometriosis did not develop malignant epithelial tumors, although one patient developed endometrioid carcinoma, grade 1, 48 months after her right laparoscopic cystectomy. The median overall survival period for all patients was 68 (range 13–131) months. Conclusion When we encounter the cases of atypical endometriosis, it is necessary to consider the possibility of ovarian cancer and carefully follow those cases for long periods.
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Affiliation(s)
- Yasuhito Tanase
- Department of obstetrics and gynecology, Nara Medical University, Nara, Japan
| | - Ryuji Kawaguchi
- Department of obstetrics and gynecology, Nara Medical University, Nara, Japan
| | - Tomoko Uchiyama
- Department of diagnostic pathology, Nara Medical University, Nara, Japan
| | - Hiroshi Kobayashi
- Department of obstetrics and gynecology, Nara Medical University, Nara, Japan
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39
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Mallen A, Soong TR, Townsend MK, Wenham RM, Crum CP, Tworoger SS. Surgical prevention strategies in ovarian cancer. Gynecol Oncol 2018; 151:166-175. [PMID: 30087058 DOI: 10.1016/j.ygyno.2018.08.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 08/02/2018] [Indexed: 12/12/2022]
Abstract
Given the current lack of effective screening for ovarian cancer, surgical removal of at-risk tissue is the most successful strategy to decrease risk of cancer development. However, the optimal timing of surgery and tissues to remove, as well as the appropriate patients to undergo preventive procedures are poorly understood. In this review, we first discuss the origin and precursors of ovarian epithelial carcinomas, focusing on high-grade serous carcinomas and endometriosis-associated carcinomas, which cause the majority of the mortality and incidence of ovarian cancer. In addition, we summarize the implications of current understanding of specific pathogenic origins for surgical prevention and remaining gaps in knowledge. Secondly, we review evidence from the epidemiologic literature on the associations of various surgical prevention strategies, including endometriosis excision, tubal procedures, and bilateral salpingo-oophorectomy, with risk of future ovarian cancer development, as well as the short- and long-term consequences of these strategies on women's health and quality and life. We conclude with recommendations for surgical prevention in women with high-risk genetic mutations and average-risk women, and a brief discussion of ongoing research that will help clarify optimal surgical approaches that balance risk-reduction with maintenance of women's quality of life.
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Affiliation(s)
- Adrianne Mallen
- Department of Gynecologic Oncology, Moffitt Cancer Center, Tampa, FL, United States of America
| | - T Rinda Soong
- Department of Pathology, University of Washington, Seattle, WA, United States of America
| | - Mary K Townsend
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States of America
| | - Robert M Wenham
- Department of Gynecologic Oncology, Moffitt Cancer Center, Tampa, FL, United States of America
| | - Christopher P Crum
- Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America
| | - Shelley S Tworoger
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States of America; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
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Abstract
Endometriosis-associated cancers include clear cell and endometrioid ovarian carcinoma. A history of endometriosis has long been considered to be a risk factor for later development of these malignancies; however, recent molecular genetic evidence has provided unequivocal evidence that these lesions are in fact the precursors for endometriosis-associated cancers. Herein, we will explore the relationship between endometriosis and ovarian carcinomas, similarities between the premalignant lesions and their cancerous counterparts, and the potential role of mutations and the ovarian microenvironment that may contribute to malignant transformation.
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41
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Oral E, Aydin O, Kumbak BA, İlvan S, Yilmaz H, Tustas E, Bese T, Demirkiran F, Arvas M. Concomitant endometriosis in malignant and borderline ovarian tumours. J OBSTET GYNAECOL 2018; 38:1104-1109. [DOI: 10.1080/01443615.2018.1441815] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- Engin Oral
- Department of Obstetrics and Gynecology, Cerrahpasa Medical School, İstanbul University, İstanbul, Turkey
| | - Ovgu Aydin
- Department of Pathology, Cerrahpasa Medical School, İstanbul University, İstanbul, Turkey
| | - Banu Aygun Kumbak
- Department of Obstetrics and Gynecology, İstanbul Aydin University, İstanbul, Turkey
| | - Sennur İlvan
- Department of Pathology, Cerrahpasa Medical School, İstanbul University, İstanbul, Turkey
| | - Handan Yilmaz
- Department of Obstetrics and Gynecology, Cerrahpasa Medical School, İstanbul University, İstanbul, Turkey
| | - Esra Tustas
- Umraniye Education and Research Hospital, İstanbul, Turkey
| | - Tugan Bese
- Department of Obstetrics and Gynecology, Cerrahpasa Medical School, İstanbul University, İstanbul, Turkey
| | - Fuat Demirkiran
- Department of Obstetrics and Gynecology, Cerrahpasa Medical School, İstanbul University, İstanbul, Turkey
| | - Macit Arvas
- Department of Obstetrics and Gynecology, Cerrahpasa Medical School, İstanbul University, İstanbul, Turkey
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Taniguchi F. New knowledge and insights about the malignant transformation of endometriosis. J Obstet Gynaecol Res 2018; 43:1093-1100. [PMID: 28718209 DOI: 10.1111/jog.13372] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 03/13/2017] [Accepted: 04/02/2017] [Indexed: 12/25/2022]
Abstract
Endometriosis may be a definitive risk factor for ovarian cancer, the most fatal gynecological cancer. The ability of endometriosis to transform into malignancy, first described by Dr. Sampson in 1925, is considered a rare occurrence, affecting approximately 1% of ovarian endometriomas. Recently we conducted a retrospective study regarding the malignant transformation of endometriosis in Japanese women. Many studies have reported a consistent correlation between endometriosis and ovarian cancer according to histological subtypes. However, the existing epidemiological evidence linking this association is insufficient to define the role of endometriosis as a cause of ovarian cancer and to influence changes to current clinical practice. Prospective cohort studies are therefore needed to clarify this issue. Additionally, the results of many molecular studies are conflicting, and earlier studies showing the molecular aberrations involved in genomic instability and mutation that enable malignant transformation have not been replicated in later studies. Careful long-term observation of a patient with endometrioma is required to detect possible subsequent incidence of malignant transformation. More importantly, a precise strategy should be set up for better prevention, early detection, specific diagnosis and treatment targeting molecular pathogenesis to understand the mechanisms of endometriosis-associated ovarian cancer. Clinicians need to be aware of the increased ovarian cancer risk in women with endometriosis.
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Affiliation(s)
- Fuminori Taniguchi
- Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Japan
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43
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The Association Between Endometriosis and Surface Epithelial Ovarian Tumors: A Review of Pathological Data. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2018. [DOI: 10.5812/ijcm.9610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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44
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Dawson A, Fernandez ML, Anglesio M, Yong PJ, Carey MS. Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development. Ecancermedicalscience 2018; 12:803. [PMID: 29456620 PMCID: PMC5813919 DOI: 10.3332/ecancer.2018.803] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Indexed: 12/11/2022] Open
Abstract
Endometriosis is a fascinating disease that we strive to better understand. Molecular techniques are shedding new light on many important aspects of this disease: from pathogenesis to the recognition of distinct disease variants like deep infiltrating endometriosis. The observation that endometriosis is a cancer precursor has now been strengthened with the knowledge that mutations that are present in endometriosis-associated cancers can be found in adjacent endometriosis lesions. Recent genomic studies, placed in context, suggest that deep infiltrating endometriosis may represent a benign neoplasm that invades locally but rarely metastasises. Further research will help elucidate distinct aberrations which result in this phenotype. With respect to identifying those patients who may be at risk of developing endometriosis-associated cancers, a combination of molecular, pathological, and inheritance markers may define a high-risk group that might benefit from risk-reducing strategies.
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Affiliation(s)
- Amy Dawson
- Department of Obstetrics & Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6Z 2K8, Canada
| | - Marta Llauradó Fernandez
- Department of Obstetrics & Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6Z 2K8, Canada
| | - Michael Anglesio
- Department of Obstetrics & Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6Z 2K8, Canada.,Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada
| | - Paul J Yong
- Department of Obstetrics & Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6Z 2K8, Canada
| | - Mark S Carey
- Department of Obstetrics & Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6Z 2K8, Canada.,Department of Surgical Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1G1, Canada
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Halim TA, Attar R, Donfrancesco C, Farooqi AA, Zaman F. From Endometriosis to Cancer: Spotlight on Intracellular Signaling Cascades and MicroRNAs. RECENT TRENDS IN CANCER BIOLOGY: SPOTLIGHT ON SIGNALING CASCADES AND MICRORNAS 2018:1-10. [DOI: 10.1007/978-3-319-71553-7_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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46
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Chang CM, Wang ML, Lu KH, Yang YP, Juang CM, Wang PH, Hsu RJ, Yu MH, Chang CC. Integrating the dysregulated inflammasome-based molecular functionome in the malignant transformation of endometriosis-associated ovarian carcinoma. Oncotarget 2017; 9:3704-3726. [PMID: 29423077 PMCID: PMC5790494 DOI: 10.18632/oncotarget.23364] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 10/29/2017] [Indexed: 11/30/2022] Open
Abstract
The coexistence of endometriosis (ES) with ovarian clear cell carcinoma (CCC) or endometrioid carcinoma (EC) suggested that malignant transformation of ES leads to endometriosis associated ovarian carcinoma (EAOC). However, there is still lack of an integrating data analysis of the accumulated experimental data to provide the evidence supporting the hypothesis of EAOC transformation. Herein we used a function-based analytic model with the publicly available microarray datasets to investigate the expression profiling between ES, CCC, and EC. We analyzed the functional regularity pattern of the three type of samples and hierarchically clustered the gene sets to identify key mechanisms regulating the malignant transformation of EAOC. We identified a list of 18 genes (NLRP3, AIM2, PYCARD, NAIP, Caspase-4, Caspase-7, Caspase-8, TLR1, TLR7, TOLLIP, NFKBIA, TNF, TNFAIP3, INFGR2, P2RX7, IL-1B, IL1RL1, IL-18) closely related to inflammasome complex, indicating an important role of inflammation/immunity in EAOC transformation. We next explore the association between these target genes and patient survival using Gene Expression Omnibus (GEO), and found significant correlation between the expression levels of the target genes and the progression-free survival. Interestingly, high expression levels of AIM2 and NLRP3, initiating proteins of inflammasomes, were significantly correlated with poor progression-free survival. Immunohistochemistry staining confirmed a correlation between high AIM2 and high Ki-67 in clinical EAOC samples, supporting its role in disease progression. Collectively, we established a bioinformatic platform of gene-set integrative molecular functionome to dissect the pathogenic pathways of EAOC, and demonstrated a key role of dysregulated inflammasome in modulating the malignant transformation of EAOC.
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Affiliation(s)
- Chia-Ming Chang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Mong-Lien Wang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Kai-Hsi Lu
- Department of Medical Research and Education, Cheng-Hsin Hospital, Taipei, Taiwan
| | - Yi-Ping Yang
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chi-Mou Juang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Peng-Hui Wang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Ren-Jun Hsu
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.,Biobank Management Center of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Mu-Hsien Yu
- Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Cheng-Chang Chang
- Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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Matias-Guiu X, Stewart CJR. Endometriosis-associated ovarian neoplasia. Pathology 2017; 50:190-204. [PMID: 29241974 DOI: 10.1016/j.pathol.2017.10.006] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 10/10/2017] [Accepted: 10/11/2017] [Indexed: 12/13/2022]
Abstract
This article reviews the most relevant pathological and molecular features of ovarian tumours that are associated with endometriosis. Endometriosis is a common condition, affecting 5-15% of all women, and it has been estimated that 0.5-1% of cases are complicated by neoplasia. The most common malignant tumours in this setting are endometrioid adenocarcinoma and clear cell adenocarcinoma, each accounting for approximately 10% of ovarian carcinomas in Western countries. A minority of cases are associated with Lynch syndrome. These carcinomas are often confined to the ovaries at presentation in which case they have relatively favourable outcomes. However, high-stage tumours, particularly clear cell carcinomas, generally have a poor prognosis and this partly reflects relative resistance to current treatment. Histological diagnosis is straightforward in the majority of cases but some variants, for example endometrioid carcinomas with sex cord-like appearances or oxyphil cells, may create diagnostic difficulty. Similarly, clear cell carcinomas can show a range of architectural and cytological patterns that overlap with other tumours, both primary and metastatic, involving the ovaries. Endometriosis-associated borderline tumours are less common, and they often show mixed patterns of differentiation (seromucinous tumours). Atypical endometriosis may represent an intermediate step in neoplastic progression and some of these lesions demonstrate immunohistological and molecular alterations similar to those observed in endometriosis-related tumours. ARID1A mutations are relatively common in all of these tumours, but each has additional characteristic molecular alterations which are likely to be of increasing clinical relevance as targeted therapies are developed. Less is known of the pathogenesis of rarer endometriosis-associated ovarian tumours including endometrioid stromal sarcoma, mesodermal (Müllerian) adenosarcoma, and carcinosarcoma. This article also briefly reviews the issue of synchronous endometrioid carcinomas of the endometrium and the ovary, including the most recent developments on pathogenesis.
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Affiliation(s)
- Xavier Matias-Guiu
- Department of Pathology, Hospital U Arnau de Vilanova and Hospital U de Bellvitge, IDIBELL, IRBLleida, University of Lleida, and CIBERONC, Spain
| | - Colin J R Stewart
- Department of Histopathology, King Edward Memorial Hospital, Perth, and School for Women's and Infants' Health, University of Western Australia, Perth, WA, Australia.
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Discovering the Deregulated Molecular Functions Involved in Malignant Transformation of Endometriosis to Endometriosis-Associated Ovarian Carcinoma Using a Data-Driven, Function-Based Analysis. Int J Mol Sci 2017; 18:ijms18112345. [PMID: 29113136 PMCID: PMC5713314 DOI: 10.3390/ijms18112345] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 11/03/2017] [Accepted: 11/04/2017] [Indexed: 12/12/2022] Open
Abstract
The clinical characteristics of clear cell carcinoma (CCC) and endometrioid carcinoma EC) are concomitant with endometriosis (ES), which leads to the postulation of malignant transformation of ES to endometriosis-associated ovarian carcinoma (EAOC). Different deregulated functional areas were proposed accounting for the pathogenesis of EAOC transformation, and there is still a lack of a data-driven analysis with the accumulated experimental data in publicly-available databases to incorporate the deregulated functions involved in the malignant transformation of EOAC. We used the microarray gene expression datasets of ES, CCC and EC downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database. Then, we investigated the pathogenesis of EAOC by a data-driven, function-based analytic model with the quantified molecular functions defined by 1454 Gene Ontology (GO) term gene sets. This model converts the gene expression profiles to the functionome consisting of 1454 quantified GO functions, and then, the key functions involving the malignant transformation of EOAC can be extracted by a series of filters. Our results demonstrate that the deregulated oxidoreductase activity, metabolism, hormone activity, inflammatory response, innate immune response and cell-cell signaling play the key roles in the malignant transformation of EAOC. These results provide the evidence supporting the specific molecular pathways involved in the malignant transformation of EAOC.
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Schnack TH, Høgdall E, Thomsen LN, Høgdall C. Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status. Int J Gynecol Cancer 2017; 27:1804-1812. [PMID: 28976447 DOI: 10.1097/igc.0000000000001102] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
OBJECTIVES Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status. METHODS Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant. RESULTS Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis (hazard ratio, 2.56 [95% confidence interval, 1.29-5.02], in the multivariate analysis. CONCLUSIONS Age at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant endometriosis develop through distinct pathogenic pathways.
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Affiliation(s)
- Tine H Schnack
- *Juliane Marie Centret, Gynaecological Clinic, University Hospital of Copenhagen, København Ø; †Department of Pathology, Molecular Unit, Herlev Hospital, Herlev; and ‡Department of Pathology, University Hospital of Copenhagen, København Ø, Denmark
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Zhu HL, Gao SY, Shen DH, Cui H. Clinicopathological Characteristics of Ten Patients with Atypical Glandular Hyperplasia Transformation of Adenomyosis. Chin Med J (Engl) 2017; 129:364-6. [PMID: 26831242 PMCID: PMC4799584 DOI: 10.4103/0366-6999.174485] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Affiliation(s)
- Hong-Lan Zhu
- Department of Obstetrics and Gynecology, People's Hospital, Peking University, Beijing 100044, China
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