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1
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Bixel KL, Meade CE, Brown M, Felix AS. Adjuvant hormone therapy and overall survival among low-grade and apparent early-stage endometrial stromal sarcoma patients. J Gynecol Oncol 2025; 36:e50. [PMID: 39727414 PMCID: PMC12099043 DOI: 10.3802/jgo.2025.36.e50] [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] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 11/03/2024] [Indexed: 12/28/2024] Open
Abstract
OBJECTIVE Surgery is the mainstay of treatment for low-grade endometrial stromal sarcoma (LG-ESS). While adjuvant hormone therapy is recommended for patients with advanced/recurrent disease, no consensus regarding its use among early-stage patients exists. We aimed to identify correlates of adjuvant hormone therapy use and associations of adjuvant hormone therapy and overall survival (OS) in stage I LG-ESS patients. METHODS Retrospective cohort study of patients with stage I LG-ESS who underwent hysterectomy from 2004-2019 using data from the National Cancer Database. Categorical data were compared using χ² tests. Kaplan-Meier estimates and log-rank tests were used to compare OS according to adjuvant hormone use. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between adjuvant hormone use and OS were estimated using Cox proportional hazards regression. RESULTS Of 2,386 patients included, 20.2% were treated with adjuvant hormonal therapy. Use of hormone therapy increased over time, with rates approximately doubling from 2004 to 2019 (12.6% to 24.6%). Age, tumor size, lymphovascular space invasion and adjuvant radiation were associated with adjuvant hormone therapy use. There was no association between adjuvant hormone therapy and OS (log-rank p=0.73; HR=1.05; 95% CI=0.76-1.46) for patients with LG-ESS. CONCLUSION Use of adjuvant hormone therapy for stage I LG-ESS has increased over time though is not associated with OS in this cohort of patients. Additional evaluation is needed to understand the impact of adjuvant hormone therapy on recurrence rates, progression rates, and quality of life to fully understand its value.
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Affiliation(s)
- Kristin L Bixel
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA.
| | - Caitlin E Meade
- Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, OH, USA
| | - Morgan Brown
- Department of Obstetrics and Gynecology, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Ashley S Felix
- Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, OH, USA
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Chen L, Liu W, Wang M, Feng Y, Xiao T, Yang Y, Huang X. Expression of REV7 has prognostic significance in cervical cancer treated with intensity-modulated radiation therapy. Discov Oncol 2025; 16:466. [PMID: 40186683 PMCID: PMC11972243 DOI: 10.1007/s12672-025-02224-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 03/24/2025] [Indexed: 04/07/2025] Open
Abstract
BACKGROUND Human cervical cancer is the fourth most common malignancies among females worldwide. Radiotherapy is crucial in the treatment of cervical cancer. REV7 is associated with the radiosensitivity of cancer cells. We aimed to investigate the relationship between the REV7 expression and the clinical outcome for patients with cervical cancer who received radiation therapy and identify new markers for studying radiosensitivity in cervical cancer. MATERIAL AND METHODS The expression of REV7 in 71 cases of cervical squamous cell carcinoma (CSCC) tissues, 20 paracancerous tissues and 20 normal cervical epithelia tissues were analyzed by qRT-PCR and immunohistochemistry (IHC). Among them, 60 patients who underwent intensity-modulated radiation therapy (IMRT) and met the inclusion and exclusion criteria were divided into groups based on the REV7 IHC score: high-expression and low-expression. The relationship between REV7 expression level and short-term efficacy, recurrence and metastasis was investigated. Meanwhile, univariate, multivariate, and Kaplan-Meier analyses were used to analyze the association of REV7 expression with disease-free survival (DFS) and overall survival (OS). RESULTS The expression of REV7 is upregulated in CSCC tissues. There was a higher likelihood of progression (pelvic recurrence or distant metastasis) in the group with high REV7 expression (P = 0.024). Moreover, the REV7-high expression patients showed a shorter DFS than the REV7-low expression group (P = 0.011). CONCLUSIONS The higher expression level of REV7 indicates an unfavorable prognosis in cervical cancer patients undergoing IMRT treatment. REV7 could potentially serve as a novel biomarker and therapeutic target for investigating the radiosensitivity of cervical cancer.
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Affiliation(s)
- Ling Chen
- Department of Radiotherapy, Changzhou Cancer Hospital, No.68 Honghe Road, Xinbei District, Changzhou, 213032, Jiangsu, China
| | - Wei Liu
- Department of Radiotherapy, Shandong Second Provincial General Hospital, Jinan, 25000, Shandong, China
| | - Meihua Wang
- Department of Pathology, Changzhou Cancer Hospital, Changzhou, 213032, Jiangsu, China
| | - Yang Feng
- Department of Oncology, Wuxi No.2 People's Hospital, Jiangnan University Medical Center, Wuxi, 214002, Jiangsu, China
| | - Tiechen Xiao
- Department of Medical Imaging, Changzhou Cancer Hospital, Changzhou, 213032, Jiangsu, China
| | - Yuxing Yang
- Department of Radiotherapy, Changzhou Cancer Hospital, No.68 Honghe Road, Xinbei District, Changzhou, 213032, Jiangsu, China.
| | - Xue Huang
- Department of Radiotherapy, Changzhou Cancer Hospital, No.68 Honghe Road, Xinbei District, Changzhou, 213032, Jiangsu, China.
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Ray-Coquard I, Casali PG, Croce S, Fennessy FM, Fischerova D, Jones R, Sanfilippo R, Zapardiel I, Amant F, Blay JY, Martἰn-Broto J, Casado A, Chiang S, Dei Tos AP, Haas R, Hensley ML, Hohenberger P, Kim JW, Kim SI, Meydanli MM, Pautier P, Abdul Razak AR, Sehouli J, van Houdt W, Planchamp F, Friedlander M. ESGO/EURACAN/GCIG guidelines for the management of patients with uterine sarcomas. Int J Gynecol Cancer 2024; 34:1499-1521. [PMID: 39322612 DOI: 10.1136/ijgc-2024-005823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2024] Open
Affiliation(s)
- Isabelle Ray-Coquard
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
- Hesper Laboratory, Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Paolo Giovanni Casali
- Medical Oncology Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
- Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
| | - Sabrina Croce
- Department of Biopathology, Institut Bergonié, Bordeaux, France
| | - Fiona M Fennessy
- Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Daniela Fischerova
- Department of Gynecology, Obstetrics and Neonatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague 2, Czech Republic
| | - Robin Jones
- Royal Marsden Hospital NHS Trust, London, UK
| | - Roberta Sanfilippo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Ignacio Zapardiel
- Gynecologic Oncology Unit, La Paz University Hospital, Madrid, Spain
| | - Frédéric Amant
- Department of Oncology, KU Leuven, Leuven, Flanders, Belgium
- Department of Gynecology, Antoni van Leeuwenhoek Nederlands Kanker Instituut afdeling Gynaecologie, Amsterdam, Netherlands
| | - Jean-Yves Blay
- Department of Medical Oncology, Centre Leon Berard, Lyon, France
| | - Javier Martἰn-Broto
- Department of Medical Oncology, Fundación Jimenez Diaz University Hospital, Madrid, Spain
- University Hospital General de Villalba, Madrid, Spain
| | - Antonio Casado
- Department of Medical Oncology, University Hospital San Carlos, Madrid, Spain
| | - Sarah Chiang
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Angelo Paolo Dei Tos
- Department of Integrated Diagnostics, Azienda Ospedale-Università Padova, Padua, Italy
- Department of Medicine, University of Padua, Padua, Italy
| | - Rick Haas
- Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam, Netherlands
- Department of Radiotherapy, Leiden University Medical Center, Leiden, Netherlands
| | - Martee L Hensley
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Medicine, Weill Cornell Medical College, New York, New York, USA
| | - Peter Hohenberger
- Division of Surgical Oncology and Thoracic Surgery, Mannheim University Medical Centre, University of Heidelberg, Mannheim, Germany
| | - Jae-Weon Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
| | - Se Ik Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
| | | | - Patricia Pautier
- Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, Île-de-France, France
| | - Albiruni R Abdul Razak
- Division of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre Gynecologic Site Group, Toronto, Ontario, Canada
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Jalid Sehouli
- Department of Gynecology with Center for Oncological Surgery, Charite Universitatsmedizin Berlin, Berlin, Germany
| | - Winan van Houdt
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, Netherlands
| | | | - Michael Friedlander
- Department of Medical Oncology, School of Clinical Medicine, Faculty of Medicine and Health, Sydney, New South Wales, Australia
- Department of Medical Oncology, Prince of Wales and Royal Hospital for Women, Randwick, New South Wales, Australia
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4
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Quan C, Zheng Z, Cao S, Wu Y, Zhang W, Huang Y. The value of surgery and the prognostic factors for patients with recurrent low-grade endometrial stromal sarcoma: a retrospective study of 38 patients. J Gynecol Oncol 2024; 35:e98. [PMID: 38725236 PMCID: PMC11262902 DOI: 10.3802/jgo.2024.35.e98] [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: 07/25/2023] [Revised: 12/18/2023] [Accepted: 03/31/2024] [Indexed: 07/22/2024] Open
Abstract
OBJECTIVE As an indolent malignant tumor, the long-term management of low-grade endometrial stromal sarcoma (LGESS) patients required awareness, especially the management of recurrences. Unfortunately, few studies focused on the treatment of recurrent LGESS. Our study aimed to investigate the prognostic factors and the value of recurrent surgery on recurrent LGESS. METHODS This retrospective study consecutively recruited patients with pathologically diagnosed recurrent LGESS at our center from April 1, 2004 to April 1, 2020. RESULTS After a median follow-up of 137.0 months (95% confidence interval=85.4-188.6), the 5-year cumulative survival rate of the cohort of 38 patients with recurrent LGESS was 71.1%. The median overall survival (OS) and post-recurrence survival (PRS) was 156 and 89.0 months. Survival analysis showed that patients with younger age, positive estrogen receptor (ER) and optimal abdominopelvic debulking in the first recurrent surgery had better prognosis (p<0.05). Multivariate analysis showed that optimal abdominopelvic debulking in the first recurrent surgery was the only independent prognostic factor for OS and PRS (OS=216.0/35.0 months, hazard ratio [HR]=5.319, p=0.034; PRS=not reached/4.0 months, HR=10.900, p=0.006). There was no significant difference in OS and PRS between patients recurred only once and those recurred at least twice (p>0.05). CONCLUSIONS The prognosis of recurrent LGESS was favorable. Optimal debulking of no residual tumor in abdominal and pelvic cavity should be the first choice of treatment for recurrent patients, while preservation of ovary or fertility should not be recommended.
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Affiliation(s)
- Chenlian Quan
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhong Zheng
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Siyu Cao
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yong Wu
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wei Zhang
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yan Huang
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Guo J, Fan J, Zhang Y, Li M, Jin Z, Shang Y, Zhang H, Kong Y. Progesterone inhibits endometrial cancer growth by inhibiting glutamine metabolism through ASCT2. Biosci Rep 2024; 44:BSR20232035. [PMID: 38415405 PMCID: PMC10932743 DOI: 10.1042/bsr20232035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 02/08/2024] [Accepted: 02/27/2024] [Indexed: 02/29/2024] Open
Abstract
Endometrial carcinoma (EC) is a common malignancy that originates from the endometrium and grows in the female reproductive system. Surgeries, as current treatments for cancer, however, cannot meet the fertility needs of young women patients. Thus, progesterone (P4) therapy is indispensable due to its effective temporary preservation of female fertility. Many cancer cells are often accompanied by changes in metabolic phenotypes, and abnormally dependent on the amino acid glutamine. However, whether P4 exerts an effect on EC via glutamine metabolism is unknown. In the present study, we found that P4 could inhibit glutamine metabolism in EC cells and down-regulate the expression of the glutamine transporter ASCT2. This regulation of ASCT2 affects the uptake of glutamine. Furthermore, the in vivo xenograft studies showed that P4 inhibited tumor growth and the expression of key enzymes involved in glutamine metabolism. Our study demonstrated that the direct regulation of glutamine metabolism by P4 and its anticancer effect was mediated through the inhibition of ASCT2. These results provide a mechanism underlying the effects of P4 therapy on EC from the perspective of glutamine metabolism.
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Affiliation(s)
- Jinqiu Guo
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | - Jianhui Fan
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | - Yaru Zhang
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | - Mengyue Li
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | - Zeen Jin
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | - Yuhong Shang
- Department of Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Hongshuo Zhang
- Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China
| | - Ying Kong
- Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
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6
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Bendimya M, Al Jarroudi O, Brahmi SA, Afqir S. A Case Report of Uterine Müllerian Adenosarcoma With Sarcomatous Overgrowth. Cureus 2024; 16:e51806. [PMID: 38322085 PMCID: PMC10846754 DOI: 10.7759/cureus.51806] [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] [Accepted: 01/07/2024] [Indexed: 02/08/2024] Open
Abstract
Uterine adenosarcoma remains a highly aggressive tumor and is less described in the literature, with an unfavorable prognosis and an increased risk of local and distant recurrence. However, surgery, chemotherapy, and radiotherapy offer local control of the disease, and overall survival remains reduced. We report the case of a 79-year-old patient with stage IIIB uterine adenosarcoma, confirmed by immunohistochemistry and initially diagnosed with postmenopausal metrorrhagia. The patient was managed through a multimodal treatment by conducting a multidisciplinary consultation.
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Affiliation(s)
- Mohammed Bendimya
- Medical Oncology, Faculty of Medicine and Pharmacy, Mohammed First University, Oujda, MAR
- Medical Oncology, Mohammed VI University Hospital Center, Oujda, MAR
| | | | - Sami Aziz Brahmi
- Medical Oncology, Mohammed VI University Hospital Center, Oujda, MAR
| | - Said Afqir
- Medical Oncology, Mohammed VI University Hospital Center, Oujda, MAR
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7
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Lebreton C, Meeus P, Genestie C, Croce S, Guyon F, Moscardo CL, Taieb S, Blay JY, Bonvalot S, Bompas E, Chevreau C, Lécuru F, Rossi L, Joly F, Rios M, Chaigneau L, Duffaud F, Pautier P, Ray-Coquard I. Sarcomes du stroma endométrial de bas grade : référentiels de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG. Bull Cancer 2023:S0007-4551(23)00141-8. [PMID: 36990895 DOI: 10.1016/j.bulcan.2023.03.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 02/08/2023] [Accepted: 03/05/2023] [Indexed: 03/29/2023]
Abstract
Low-grade endometrial stromal sarcoma (LG-ESS) accounts for approximately 15% of all uterine sarcomas. Median age of patients is around 50 years and half of the patients are premenopausal. In all, 60% of cases present with FIGO stage I disease. Preoperatively radiologic findings of ESS are not specific. Pathological diagnosis remains essential. This review aimed to present the French guidelines for low grade ESS treatment within the Groupe sarcome français - Groupe d'étude des tumeurs osseuse (GSF-GETO)/NETSARC+ and tumeur maligne rare gynécologique (TMRG) networks. Treatments should be validated in multidisciplinary team involved in sarcomas or rare gynecologic tumors. Hysterectomy is the cornerstone of treatment for localized ESS, and morcellation should be avoided. Systematic lymphadenectomy in ESS does not improve the outcome and is not recommended. Leaving the ovaries in situ in stage I tumors could be discussed for young women. Adjuvant hormonal treatment could be considered, for two years for stage I with morcellation or stage II and livelong for stages III or IV. Nevertheless, several questions remain, such as optimal doses, regimens (progestins or aromatase inhibitors) and duration of therapy. Tamoxifen is contraindicated. Secondary cytoreductive surgery if feasible for recurrent disease, appears to be an acceptable approach. Systemic treatment for recurrent or metastatic disease is mainly hormonal, with or without surgery.
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Affiliation(s)
- Coriolan Lebreton
- Institut Bergonié, département d'oncologie médicale, 33000 Bordeaux, France; Centre Léon-Bérard, département d'oncologie médicale, 69008 Lyon, France.
| | - Pierre Meeus
- Centre Léon-Bérard, département de chirurgie, 69008 Lyon, France
| | - Catherine Genestie
- Gustave Roussy Cancer Campus, service de biopathologie, 94805 Villejuif, France
| | - Sabrina Croce
- Institut Bergonié, département de biopathologie, 33076 Bordeaux, France
| | - Frédéric Guyon
- Institut Bergonié, département de chirurgie, 33000 Bordeaux, France
| | - Carmen Llacer Moscardo
- Institut du cancer de Montpellier (ICM), département de radiothérapie oncologique, 208, avenue des Apothicaires, parc euromédecine, 34298 Montpellier cedex 5, France
| | - Sophie Taieb
- Centre Oscar Lambret, département de radiologie, 59000 Lille, France
| | - Jean-Yves Blay
- Centre Léon-Bérard, département d'oncologie médicale, 69008 Lyon, France; Université Claude Bernard Lyon 1, health services and performance research lab (EA 7425 HESPER), 69008 Lyon, France
| | - Sylvie Bonvalot
- Institut Curie, département de chirurgie oncologique, 75005 Paris, France
| | | | | | - Fabrice Lécuru
- Institut Curie, département de chirurgie oncologique, 75005 Paris, France
| | - Léa Rossi
- Centre Léon-Bérard, département de chirurgie, 69008 Lyon, France
| | - Florence Joly
- U1086 Anticipe, université Unicaen, Normandie, département oncologie médicale CLCC François Baclesse, Caen, France
| | - Maria Rios
- Institut de cancérologie de Lorraine Alexis Vautrin, département oncologie médicale, 54519 Vandœuvre-lès-Nancy, France
| | | | - Florence Duffaud
- AP-HM, hôpitaux universitaires de Marseille Timone, département d'oncologie médicale, 13005 Marseille, France
| | - Patricia Pautier
- Saclay université, Institut Gustave-Roussy, Cancer Campus, département de médecine, Villejuif, France
| | - Isabelle Ray-Coquard
- Centre Léon-Bérard, département d'oncologie médicale, 69008 Lyon, France; Université Claude Bernard Lyon 1, health services and performance research lab (EA 7425 HESPER), 69008 Lyon, France
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8
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Muacevic A, Adler JR, Alamry RF, Albahrani ZS, Alismail MA, Elghoneimy YA. Multidisciplinary Approach for a Rare Metastatic Low-Grade Endometrial Stromal Sarcoma to the Inferior Vena Cava and the Right Atrium. Cureus 2022; 14:e32807. [PMID: 36694531 PMCID: PMC9860203 DOI: 10.7759/cureus.32807] [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] [Accepted: 12/21/2022] [Indexed: 12/24/2022] Open
Abstract
Endometrial stromal sarcoma (ESS) is a rare, malignant tumor of the endometrium. Low-grade endometrial stromal sarcoma (LG-ESS) is a less aggressive subtype of ESS that rarely metastasizes to the heart and large blood vessels. In the present study, we report a case of recurrent LG-ESS after treating the initial mass in the uterus six years ago in a 49-year-old female who presented with a four-month history of dyspnea and easy fatigability. Investigations revealed a right pulmonary embolism, suspicious right psoas muscle mass, and a large inferior vena cava (IVC) thrombus. One month later, she presented with multiple gastrointestinal symptoms and weight loss. Investigations then showed the development of a new right atrial mass, infra-diaphragmatic metastatic lymphadenopathy, progression of the presacral soft tissue component, invasion of the ileal bowel loop, and a tumoral thrombus in the IVC besides new metastatic lymphadenopathy and pulmonary metastasis. Therefore, a multidisciplinary team, which had a crucial role in this complicated case, decided to commence chemotherapy treatment. Such an unusual aggressive metastatic course of LG-ESS is limited in the literature; herein, we recognize a rarely documented disease.
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9
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Denschlag D, Ackermann S, Battista MJ, Cremer W, Egerer G, Fehr M, Follmann M, Haase H, Harter P, Hettmer S, Horn LC, Juhasz-Boess I, Kast K, Köhler G, Kröncke T, Lindel K, Mallmann P, Meyer-Steinacker R, Mustea A, Petru E, Reichardt P, Schmidt D, Strauss HG, Thiel F, Ulrich UA, Vogl T, Vordermark D, Wallwiener M, Gass P, Beckmann MW. Sarcoma of the Uterus. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/074, April 2021). Geburtshilfe Frauenheilkd 2022; 82:1337-1367. [PMID: 36467974 PMCID: PMC9715351 DOI: 10.1055/a-1897-5124] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 07/11/2022] [Indexed: 12/05/2022] Open
Abstract
Purpose This is an official guideline, published and coordinated by the Germany Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management and therefore require a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is once again the result of the consensus of a representative interdisciplinary committee of experts who were commissioned by the Guidelines Committee of the DGGG to carry out a systematic search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus after a structured consensus process. Recommendations 1.1 Epidemiology, classification, staging of uterine sarcomas. 1.2 Symptoms, general diagnostic workup, general pathology or genetic predisposition to uterine sarcomas. 2. Management of leiomyosarcomas. 3. Management of low-grade endometrial stromal sarcomas. 4. Management of high-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas. 5. Management of adenosarcomas. 6. Rhabdomyosarcomas of the uterus in children and adolescents. 7. Follow-up of uterine sarcomas. 8. Management of morcellated uterine sarcomas. 9. Information provided to patients.
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Affiliation(s)
| | | | - Marco Johannes Battista
- Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und Frauengesundheit, Mainz, Germany
| | | | | | | | | | | | - Philipp Harter
- Klinik für Gynäkologie und Gynäkologische Onkologie, Kliniken Essen Mitte, Essen, Germany
| | | | - Lars-Christian Horn
- Abteilung für Mamma-, Urogenital, und Perinatalpathologie, Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Germany
| | | | - Karin Kast
- Nationales Zentrum für Familiäre Tumorerkrankungen (NCFT), Universitätsklinikum Köln, Köln, Germany
| | - Günter Köhler
- Deutsches klinisches Kompetenzzentrum für genitale Sarkome und Mischtumoren, Universitätsmedizin Greifswald, Greifswald, Germany
| | - Thomas Kröncke
- Klinik für Radiologie, Klinikum Augsburg, Augsburg, Germany
| | - Katja Lindel
- Klinik für Radioonkologie, Klinikum Karlsruhe, Karlsruhe, Germany
| | - Peter Mallmann
- Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Köln, Köln, Germany
| | | | - Alexander Mustea
- Klinik für Gynäkologie und Gynäkologische Onkologie, Universitätsklinikum Bonn, Bonn, Germany
| | - Edgar Petru
- Univ. Klinik für Frauenheilkunde und Geburtshilfe der Medizinischen Universität Graz, Graz, Austria
| | - Peter Reichardt
- Klinik für interdisziplinäre Onkologie, Helios Kliniken Berlin-Buch, Berlin, Germany
| | - Dietmar Schmidt
- MVZ für Histologie, Zytologie und Molekulare Diagnostik, Trier, Germany
| | - Hans-Georg Strauss
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Halle, Halle/Saale, Germany
| | - Falk Thiel
- Frauenklinik, Alb Fils Kliniken, Göppingen, Germany
| | - Uwe Andreas Ulrich
- Klinik für Gynäkologie und Geburtshilfe, Martin Luther Krankenhaus Berlin, Johannesstift Diakonie, Berlin, Germany
| | - Thomas Vogl
- Institut für diagnostische und interventionelle Radiologie, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany
| | - Dirk Vordermark
- Universitätsklinik und Poliklinik für Strahlentherapie, Universitätsklinikum Halle, Halle/Saale, Germany
| | | | - Paul Gass
- Frauenklinik des Universitätsklinikums Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Comprehensive Cancer Center Erlangen/Europäische Metropolregion Nürnberg
(CCC ER-EMN), Erlangen, Germany
| | - Matthias W. Beckmann
- Frauenklinik des Universitätsklinikums Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Comprehensive Cancer Center Erlangen/Europäische Metropolregion Nürnberg
(CCC ER-EMN), Erlangen, Germany
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10
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Huang X, Peng P. Hormone Therapy Reduces Recurrence in Stage II-IV Uterine Low-Grade Endometrial Stromal Sarcomas: A Retrospective Cohort Study. Front Oncol 2022; 12:922757. [PMID: 35837098 PMCID: PMC9275776 DOI: 10.3389/fonc.2022.922757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 05/30/2022] [Indexed: 11/23/2022] Open
Abstract
Low-grade endometrial stromal sarcoma (LG-ESS) is a rare and indolent malignancy. Hormone therapy has been reported as an adjuvant treatment for LG-ESS, although its effectiveness is controversial. Here we aimed to investigate the effects of postoperative hormone therapy on recurrence in patients with uterine LG-ESS. Between January 2010 and December 2019, a total of 152 patients (23 with and 129 without fertility-sparing) with a diagnosis of primary uterine LG-ESS confirmed by pathologists were enrolled in this study. In the cohort without fertility-sparing, 22 (17.7%) patients had recurrence, and the median disease-free survival (DFS) was 47 (2-130) months; only one of these patients died of LG-ESS. No significant difference was found in recurrence between the groups with and without hormone therapy (p=0.802). However, subgroup analysis showed that hormone therapy decreased the recurrence rate in stage II-IV (p=0.001, HR 0.144, 95% CI: 0.038-0.548), but not in stage I disease (p=0.256). High-dose progestins notably reduced recurrence (p=0.012, HR 0.154, 95% CI: 0.036-0.660), whereas non-progestin therapy marginally influenced recurrence (p=0.054) compared with no hormone therapy in stage II-IV disease. Moreover, hormone therapy within 12 months was effective in reducing recurrence (p=0.038, HR 0.241, 95% CI: 0.063-0.922). Ovarian preservation (p=0.004, HR 6.250, 95% CI: 1.786-21.874) and negative expression of ER/PR (p=0.000, HR 23.249, 95% CI: 4.912-110.026) were high-risk factors for recurrence in patients without fertility-sparing. In the fertility-sparing cohort, 15 (65.2%) patients experienced recurrence, and the median DFS was 24 (3-107) months. Six patients successfully delivered healthy fetuses, and five received hormone therapy. Twelve patients finally accepted hysterectomy after repeated recurrence, and only two of them had given birth before surgery. Patients who received hormone therapy showed longer DFS, although this difference was not statistically significant (p=0.466). In conclusion, postoperative hormone therapy reduces recurrence in patients with stage II–IV uterine LG-ESS without fertility-sparing, and high-dose treatment with progestins within 12 months is recommended. Bilateral oophorectomy can also reduce the risk of recurrence. Patients with fertility-sparing have a high risk of recurrence and poor pregnancy outcomes, and hormone therapy may be a reasonable choice in postoperative management.
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11
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Maccaroni E, Lunerti V, Agostinelli V, Giampieri R, Zepponi L, Pagliacci A, Berardi R. New Insights into Hormonal Therapies in Uterine Sarcomas. Cancers (Basel) 2022; 14:921. [PMID: 35205669 PMCID: PMC8870116 DOI: 10.3390/cancers14040921] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/02/2022] [Accepted: 02/08/2022] [Indexed: 02/06/2023] Open
Abstract
Uterine sarcoma (US) is a rare mesenchymal malignant cancer type, accounting for 3-7% of uterine malignancies. US prognosis is still poor due to high local and distant recurrence rates. As for molecular features, US may present variable oestrogen receptor (ER) and progesterone receptor (PR) expressions, mostly depending on histotype and grading. Surgery represents the mainstay of treatment for early-stage disease, while the role of adjuvant chemotherapy or local radiotherapy is still debated and defined on the basis of histotype, tumour grading and stage. In metastatic setting, uterine sarcomas' treatment includes palliative surgery, a metastases resection, chemotherapy, hormonal therapy and targeted therapy. As for the chemotherapy regimen used, drugs that are considered most effective are doxorubicin (combined with ifosfamide or alone), gemcitabine combined with docetaxel and, more recently, trabectedin or pazopanib. Hormonal therapies, including aromatase inhibitors (AIs), progestins and gonadotropin-releasing hormone analogues (GnRH-a) may also represent an effective option, in particular for low-grade endometrial stromal sarcoma (LGESS), due to their favourable toxicity profile and patients' compliance, while their role is still under investigation in uterine leiomyosarcoma (uLMS), high-grade endometrial stromal sarcoma (HGESS), undifferentiated uterine sarcoma (USS) and other rarer US. The present review aims to analyse the existing evidence and future perspectives on hormonal therapies in US, in order to clarify their potential role in daily clinical practice.
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Affiliation(s)
- Elena Maccaroni
- Department of Oncology, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy; (L.Z.); (A.P.)
| | - Valentina Lunerti
- Department of Oncology, Università Politecnica delle Marche, 60126 Ancona, Italy; (V.L.); (V.A.)
| | - Veronica Agostinelli
- Department of Oncology, Università Politecnica delle Marche, 60126 Ancona, Italy; (V.L.); (V.A.)
| | - Riccardo Giampieri
- Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy; (R.G.); (R.B.)
| | - Laura Zepponi
- Department of Oncology, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy; (L.Z.); (A.P.)
| | - Alessandra Pagliacci
- Department of Oncology, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy; (L.Z.); (A.P.)
| | - Rossana Berardi
- Department of Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy; (R.G.); (R.B.)
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12
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Nath AG, Suchetha S, Rema PN, Sivarenjith J, John ER, Mony RP. Endometrial Stromal Sarcoma, an Unusual Recurrence: A Case Report. J Obstet Gynaecol India 2021; 71:448-451. [PMID: 34566308 DOI: 10.1007/s13224-021-01442-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 01/12/2021] [Indexed: 11/24/2022] Open
Affiliation(s)
- Aswathy G Nath
- Division of Gynaecological Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala India
| | - Sambasivan Suchetha
- Division of Gynaecological Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala India
| | - Prabhakaran Nair Rema
- Division of Gynaecological Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala India
| | - Jayapalan Sivarenjith
- Division of Surgical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala India
| | - Elizabeth Reshmi John
- Division of Surgical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala India
| | - Rari P Mony
- Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala India
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13
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Candidate Biomarkers for Specific Intraoperative Near-Infrared Imaging of Soft Tissue Sarcomas: A Systematic Review. Cancers (Basel) 2021; 13:cancers13030557. [PMID: 33535618 PMCID: PMC7867119 DOI: 10.3390/cancers13030557] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 01/16/2021] [Accepted: 01/21/2021] [Indexed: 12/27/2022] Open
Abstract
Simple Summary Near-infrared imaging of tumors during surgery facilitates the oncologic surgeon to distinguish malignant from healthy tissue. The technique is based on fluorescent tracers binding to tumor biomarkers on malignant cells. Currently, there are no clinically available fluorescent tracers that specifically target soft tissue sarcomas. This review searched the literature to find candidate biomarkers for soft tissue sarcomas, based on clinically used therapeutic antibodies. The search revealed 7 biomarkers: TEM1, VEGFR-1, EGFR, VEGFR-2, IGF-1R, PDGFRα, and CD40. These biomarkers are abundantly present on soft tissue sarcoma tumor cells and are already being targeted with humanized monoclonal antibodies. The conjugation of these antibodies with a fluorescent dye will yield in specific tracers for image-guided surgery of soft tissue sarcomas to improve the success rates of tumor resections. Abstract Surgery is the mainstay of treatment for localized soft tissue sarcomas (STS). The curative treatment highly depends on complete tumor resection, as positive margins are associated with local recurrence (LR) and prognosis. However, determining the tumor margin during surgery is challenging. Real-time tumor-specific imaging can facilitate complete resection by visualizing tumor tissue during surgery. Unfortunately, STS specific tracers are presently not clinically available. In this review, STS-associated cell surface-expressed biomarkers, which are currently already clinically targeted with monoclonal antibodies for therapeutic purposes, are evaluated for their use in near-infrared fluorescence (NIRF) imaging of STS. Clinically targeted biomarkers in STS were extracted from clinical trial registers and a PubMed search was performed. Data on biomarker characteristics, sample size, percentage of biomarker-positive STS samples, pattern of biomarker expression, biomarker internalization features, and previous applications of the biomarker in imaging were extracted. The biomarkers were ranked utilizing a previously described scoring system. Eleven cell surface-expressed biomarkers were identified from which 7 were selected as potential biomarkers for NIRF imaging: TEM1, VEGFR-1, EGFR, VEGFR-2, IGF-1R, PDGFRα, and CD40. Promising biomarkers in common and aggressive STS subtypes are TEM1 for myxofibrosarcoma, TEM1, and PDGFRα for undifferentiated soft tissue sarcoma and EGFR for synovial sarcoma.
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Shushkevich A, Thaker PH, Littell RD, Shah NA, Chiang S, Thornton K, Hensley ML, Slomovitz BM, Holcomb KM, Leitao MM, Toboni MD, Powell MA, Levine DA, Dowdy SC, Klopp A, Brown J. State of the science: Uterine sarcomas: From pathology to practice. Gynecol Oncol 2020; 159:3-7. [PMID: 32839026 DOI: 10.1016/j.ygyno.2020.08.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
| | - Premal H Thaker
- Washington University School of Medicine, St. Louis, MO, United States
| | - Ramey D Littell
- Kaiser Permanente Northern California Gynecologic Cancer Program, San Francisco, CA, United States
| | | | - Sarah Chiang
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | | | - Martee L Hensley
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | | | - Kevin M Holcomb
- Weill Cornell Medical College at New York-Presbyterian Hospital, New York, NY, United States
| | - Mario M Leitao
- Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Michael D Toboni
- Washington University School of Medicine, St. Louis, MO, United States
| | - Matthew A Powell
- Washington University School of Medicine, St. Louis, MO, United States
| | - Douglas A Levine
- Perlmutter Cancer Center, NYU Langone Health, New York, NY, United States
| | | | - Ann Klopp
- The University of Texas M.D., Anderson Cancer Center, Houston, TX, United States
| | - Jubilee Brown
- Levine Cancer Institute, Atrium Health, Charlotte, NC, United States.
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15
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Optimization of the Therapeutic Approach to Patients with Sarcoma: Delphi Consensus. Sarcoma 2019; 2019:4351308. [PMID: 31975783 PMCID: PMC6959159 DOI: 10.1155/2019/4351308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 09/30/2019] [Accepted: 11/06/2019] [Indexed: 02/06/2023] Open
Abstract
Soft tissue sarcomas (STS) constitute a heterogeneous group of rare solid tumors associated with significant morbidity and mortality. The evaluation and treatment of STS require a multidisciplinary team with extensive experience in the management of these types of tumors. National and international clinical practice guidelines for STS do not always provide answers to a great many situations that specialists have to contend with in their everyday practice. This consensus provides a series of specific recommendations based on available scientific evidence and the experience of a group of experts to assist in decision-making by all the specialists involved in the management of STS.
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16
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Pannier D, Cordoba A, Ryckewaert T, Robin YM, Penel N. Hormonal therapies in uterine sarcomas, aggressive angiomyxoma, and desmoid-type fibromatosis. Crit Rev Oncol Hematol 2019; 143:62-66. [DOI: 10.1016/j.critrevonc.2019.08.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 08/23/2019] [Accepted: 08/28/2019] [Indexed: 10/26/2022] Open
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17
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Denschlag D, Ackermann S, Battista MJ, Cremer W, Egerer G, Follmann M, Haas H, Harter P, Hettmer S, Horn LC, Juhasz-Boess I, Kast K, Köhler G, Kröncke T, Lindel K, Mallmann P, Meyer-Steinacker R, Mustea A, Petru E, Reichardt P, Schmidt D, Strauss HG, Tempfer C, Thiel F, Ulrich U, Vogl T, Vordermark D, Gass P, Beckmann MW. Sarcoma of the Uterus. Guideline of the DGGG and OEGGG (S2k Level, AWMF Register Number 015/074, February 2019). Geburtshilfe Frauenheilkd 2019; 79:1043-1060. [PMID: 31656317 PMCID: PMC6805182 DOI: 10.1055/a-0882-4116] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 03/22/2019] [Indexed: 12/21/2022] Open
Abstract
Aims This is an official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of how they should be managed clinically, and treatment requires a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is the result of the consensus of a representative interdisciplinary group of experts who carried out a systematic search of the literature on uterine sarcomas in the context of the guidelines program of the DGGG, OEGGG and SGGG. Members of the participating professional societies achieved a formal consensus after a moderated structured consensus process. Recommendations The consensus-based recommendations and statements include the epidemiology, classification, staging, symptoms, general diagnostic work-up and general pathology of uterine sarcomas as well as the genetic predisposition to develop uterine sarcomas. Also included are statements on the management of leiomyosarcomas, (low and high-grade) endometrial stromal sarcomas and undifferentiated uterine sarcomas and adenosarcomas. Finally, the guideline considers the follow-up and morcellation of uterine sarcomas and the information provided to patients.
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Affiliation(s)
| | | | - Marco Johannes Battista
- Universitätsmedizin Mainz, Klinik und Poliklinik für Geburtshilfe und Frauengesundheit, Mainz, Germany
| | | | | | | | | | - Philipp Harter
- Klinik für Gynäkologie und Gynäkologische Onkologie, Kliniken Essen Mitte, Essen, Germany
| | | | - Lars-Christian Horn
- Abteilung für Mamma-, Urogenital, und Perinatalpathologie, Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Germany
| | - Ingolf Juhasz-Boess
- Klinik für Gynäkologie, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
| | - Karin Kast
- Universitätsklinik Dresden, Dresden, Germany
| | - Günter Köhler
- Deutsches klinisches Kompetenzzentrum für genitale Sarkome und Mischtumoren, Universitätsmedizin Greifswald, Greifswald, Germany
| | - Thomas Kröncke
- Klinik für Radiologie, Klinikum Augsburg, Augsburg, Germany
| | - Katja Lindel
- Klinik für Radioonkologie, Klinikum Karlsruhe, Karlsruhe, Germany
| | - Peter Mallmann
- Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Köln, Köln, Germany
| | | | | | - Edgar Petru
- Universitäts-Frauenklinik Graz, Graz, Austria
| | - Peter Reichardt
- Klinik für interdisziplinäre Onkologie, Helios Kliniken Berlin-Buch, Berlin, Germany
| | | | - Hans-Georg Strauss
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Halle, Halle/Saale, Germany
| | | | - Falk Thiel
- Frauenklinik, Alb Fils Kliniken, Göppingen, Germany
| | - Uwe Ulrich
- Klinik für Gynäkologie und Geburtshilfe, Martin-Luther-Krankenhaus Berlin, Paul Gerhardt Diakonie, Berlin, Germany
| | - Thomas Vogl
- Institut für diagnostische und interventionelle Radiologie, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany
| | - Dirk Vordermark
- Universitätsklinik und Poliklinik für Strahlentherapie, Universitätsklinikum Halle, Halle/Saale, Germany
| | - Paul Gass
- Frauenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, Germany
| | - Matthias W. Beckmann
- Frauenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg; Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, Germany
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18
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Park NC, Han SJ, Lee JW, Choi HJ, Kim EJ, Jung MH, Jang JB, Hwang DS, Kim KS. Apoptotic effect of Gyejibokryunghwan on uterine sarcoma cells (SK-UT-1B). PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 61:152806. [PMID: 31035046 DOI: 10.1016/j.phymed.2018.12.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 12/18/2018] [Accepted: 12/23/2018] [Indexed: 06/09/2023]
Abstract
BACKGROUND Diagnosis of uterine sarcomais is a challenging task for clinicians because its position is not easily accessible by current conventional techniques. In addition, standardized treatment for uterine sarcoma has not yet been established due to its rarity and heterogeneity. HYPOTHESIS/PURPOSE We investigated the apoptotic cell death of uterine sarcoma cells (SK-UT-1B) induced by Gyejibokryunghwan (GBH). GBH, an herbal medicine, has been widely used for gynecological diseases in Koean medicine. METHODS SK-UT-1B cells were treated with GBH of varying concentrations from 0 to 500 µg/ml. The mechanism of cell death was investigated through multiple analysis methods, including flow cytometry, cell cycle, and western blotting. RESULTS Flow cytometric analysis revealed that the number of apoptotic cells increased in a GBH dose-dependent manner. The cell populations of sub-G1 and G0/G1 phases were increased by GBH treatment, indicating apoptosisand cell arrest, while the population of S and G2/M phases decreased. With GBH, the expression levels of cleaved caspase-3, -6, and -9 were upregulated, while the expression levels of pro-caspase-3, -6, and -9 were down-regulated in SK-UT-1B cells. CONCLUSION These results are the first observation of uterine sarcoma cell death induced by GBH and confirmation of the mechanism of cell death, which occurred through the intrinsic apoptotic pathway. Clinically, uterine sarcoma has a poor prognosis with no appropriate treatment. GBH may become a new treatment modality for uterine sarcoma.
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Affiliation(s)
- Nam Chun Park
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea
| | - Se Jik Han
- Department of Medical Engineering, Graduate school, Kyung HeeUniversity, Seoul 02447, Korea; Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul 02447, Korea
| | - Jin-Woo Lee
- Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Korea
| | - Hyuck Jai Choi
- East-West Medical Research Institute, Kyung Hee University Medical Center, Seoul 02447, Korea
| | - Eun-Jin Kim
- East-West Medical Research Institute, Kyung Hee University Medical Center, Seoul 02447, Korea
| | - Min-Hyung Jung
- Department of Obstetrics & Gynecology, School of Medicine, Kyung Hee University, Kyung Hee Medical Center, Seoul 02447, Korea
| | - Jun-Bock Jang
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea; Department of Obstetrics & Gynecology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Deok-Sang Hwang
- Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea; East-West Medical Research Institute, Kyung Hee University Medical Center, Seoul 02447, Korea; Department of Obstetrics & Gynecology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
| | - Kyung Sook Kim
- Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul 02447, Korea.
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19
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Rizzo A, Pantaleo MA, Saponara M, Nannini M. Current status of the adjuvant therapy in uterine sarcoma: A literature review. World J Clin Cases 2019; 7:1753-1763. [PMID: 31417921 PMCID: PMC6692269 DOI: 10.12998/wjcc.v7.i14.1753] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 05/16/2019] [Accepted: 06/27/2019] [Indexed: 02/05/2023] Open
Abstract
Uterine sarcomas (US) are rare mesenchymal tumours accounting approximately for 3%–7% of all uterine cancers. Histologically, US are classified into mesenchymal tumours or mixed epithelial and mesenchymal tumours. The group of mesenchymal tumours includes uterine leiomyosarcoma (uLMS, 65% of cases), endometrial stromal sarcoma (ESS, 21%) – traditionally divided into low grade (LG-ESS) and high grade–undifferentiated uterine sarcoma (5%) and other rare subtypes such as alveolar or embryonal rhabdomyosarcoma. Despite the fact that several drugs demonstrated clinical activity in advanced or metastatic settings, the role of postoperative therapy in US remains controversial. In this review, we have summarised the current state of the art, including the chief trials on adjuvant treatment modalities in US, especially focusing on uLMS, LG-ESS and other rare histotypes.
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Affiliation(s)
- Alessandro Rizzo
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy
| | - Maria Abbondanza Pantaleo
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy
| | - Maristella Saponara
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy
| | - Margherita Nannini
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40138, Italy
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20
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Nasioudis D, Ko EM, Kolovos G, Vagios S, Kalliouris D, Giuntoli RL. Ovarian preservation for low-grade endometrial stromal sarcoma: a systematic review of the literature and meta-analysis. Int J Gynecol Cancer 2019; 29:126-132. [PMID: 30640694 DOI: 10.1136/ijgc-2018-000063] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 10/15/2018] [Accepted: 10/26/2018] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVE To evaluate the effect of ovarian preservation on oncologic outcomes for women with low-grade endometrial stromal sarcoma of the uterus. METHODS A systematic search of the Medline, Embase, Cohrane, and Web of Science databases was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies including patients with low-grade endometrial stromal sarcoma who had hysterectomy were identified. Data on tumor recurrence and death rate were pooled using a random effects model. RESULTS A total of 17 studies met the inclusion criteria and reported on 786 patients. Based on available information, ovarian preservation was noted in 190 patients while 501 had bilateral salpingo-oophorectomy. A significantly increased tumor recurrence rate was observed in the ovarian preservation group (89/190, 46.8%) compared with the bilateral salpingo-oophorectomy group (121/501, 24.2%) (OR 2.70, 95% CI 1.39 to 5.28). Based on data from 162 patients, no difference in death rate was noted between the ovarian preservation (2/34, 5.9%) and bilateral salpingo-oophorectomy (9/128, 7%) groups (OR 0.80, 95% CI 0.18 to 3.47). CONCLUSIONS Approximately one-quarter of patients with low-grade endometrial stromal sarcoma were managed with ovarian preservation. These women experienced a higher recurrence rate. Hormone exposure may be responsible for this elevated risk. Given the apparent high salvage rate, however, ovarian preservation may be an option only in a well-informed patient population.
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Affiliation(s)
- Dimitrios Nasioudis
- Division of Gynecologic Oncology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
- Surgery Working Group, Obstetrics and Gynecology Subgroup, Society of Junior Doctors, Athens, Greece
| | - Emily M Ko
- Division of Gynecologic Oncology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
| | - Georgios Kolovos
- Surgery Working Group, Obstetrics and Gynecology Subgroup, Society of Junior Doctors, Athens, Greece
| | - Stylianos Vagios
- Surgery Working Group, Obstetrics and Gynecology Subgroup, Society of Junior Doctors, Athens, Greece
| | - Dimitrios Kalliouris
- Surgery Working Group, Obstetrics and Gynecology Subgroup, Society of Junior Doctors, Athens, Greece
| | - Robert L Giuntoli
- Division of Gynecologic Oncology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA
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21
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Thiel FC, Halmen S. Low-Grade Endometrial Stromal Sarcoma - a Review. Oncol Res Treat 2018; 41:687-692. [PMID: 30317238 DOI: 10.1159/000494225] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 10/02/2018] [Indexed: 12/21/2022]
Abstract
Like other uterine sarcomas, low-grade endometrial stromal sarcomas (LG-ESS) are a very rare tumor entity. In the past, research studies therefore discussed the various different types of the disease in combination. In addition, the classification of endometrial stromal tumors presented difficulties for quite some time so that in earlier studies it was not always possible to precisely distinguish between LG-ESS, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. For LG-ESS, surgery with hysterectomy and adnexectomy is the first-line treatment. The benefits of lymphadenectomy and tumor debulking are unclear. Endocrine therapy with gestagens and aromatase inhibitors is under discussion to provide adjuvant treatment for patients with advanced stages of the disease. As radiotherapy only provides locoregional control, and in view of the usually good prognosis of patients with LG-ESS, its benefits need to be weighed against its side effects. In the case of recurrence, repeat surgery is the first choice. Further research studies viewing LG-ESS as a distinct entity are needed in order to improve treatment options for patients with LG-ESS.
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Michael Straughn J, Boitano T, Smith HJ, Dilley SE, Liang MI, Novak L. Treatment of low-grade endometrial stromal sarcoma in a nulligravid woman. Gynecol Oncol 2018; 151:6-9. [PMID: 29887484 DOI: 10.1016/j.ygyno.2018.05.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
A 32 year-old nulligravid woman with a uterine mass underwent exploratory laparotomy with myomectomy. Final pathology revealed a low-grade endometrial stromal sarcoma (ESS) with positive margins. She subsequently underwent definitive robotic hysterectomy and bilateral salpingectomy with ovarian preservation. She was diagnosed with a stage IB low-grade ESS. She is currently undergoing observation. Discussion of classification, surgical options, and adjuvant therapy is presented.
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Affiliation(s)
- J Michael Straughn
- University of Alabama at Birmingham, Division of Gynecologic Oncology, United States.
| | - Teresa Boitano
- University of Alabama at Birmingham, Division of Gynecologic Oncology, United States
| | - Haller J Smith
- University of Alabama at Birmingham, Division of Gynecologic Oncology, United States
| | - Sarah E Dilley
- University of Alabama at Birmingham, Division of Gynecologic Oncology, United States
| | - Margaret I Liang
- University of Alabama at Birmingham, Division of Gynecologic Oncology, United States
| | - Lea Novak
- University of Alabama at Birmingham, Department of Pathology, United States
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Deshmukh U, Black J, Perez-Irizarry J, Passarelli R, Levy K, Rostkowski A, Hui P, Rutherford TJ, Santin AD, Azodi M, Silasi DA, Ratner E, Litkouhi B, Schwartz PE. Adjuvant Hormonal Therapy for Low-Grade Endometrial Stromal Sarcoma. Reprod Sci 2018; 26:600-608. [DOI: 10.1177/1933719118778801] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Uma Deshmukh
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Jonathan Black
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Javier Perez-Irizarry
- Yale-New Haven Hospital-Smilow Cancer Center Tumor Registry, Yale University School of Medicine, New Haven, CT, USA
| | | | - Karen Levy
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Amanda Rostkowski
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Pei Hui
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Thomas J. Rutherford
- College of Medicine Obstetrics & Gynecology, University of South Florida, Tampa, FL, USA
| | - Alessandro D. Santin
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Masoud Azodi
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Dan-Arin Silasi
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Elena Ratner
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Babak Litkouhi
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Peter E. Schwartz
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
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Desar IME, Ottevanger PB, Benson C, van der Graaf WTA. Systemic treatment in adult uterine sarcomas. Crit Rev Oncol Hematol 2017; 122:10-20. [PMID: 29458779 DOI: 10.1016/j.critrevonc.2017.12.009] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 12/12/2017] [Indexed: 12/28/2022] Open
Abstract
Uterine sarcomas (US) are rare mesenchymal tumours of the uterus and are divided mainly into uterine leiomyosarcoma (uLMS), low grade endometrial stromal sarcoma (LG-ESS), high grade endometrial stromal sarcoma (HG-ESS), adenosarcomas and high grade undifferentiated sarcoma (HGUS). US are often high-grade tumours with a high local recurrence rate and metastatic risk. We here discuss the current standard of care and knowledge of systemic therapy for adult uterine sarcomas, in particular uLMS, LG-ESS, HG-ESS and HGUS, in both the adjuvant as well as the metastatic setting.
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Affiliation(s)
- I M E Desar
- Department of Medical Oncology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - P B Ottevanger
- Department of Medical Oncology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
| | - C Benson
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - W T A van der Graaf
- Department of Medical Oncology, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands; The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, Sutton, London, United Kingdom.
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25
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Li H, Li M, Pang Y, Liu F, Sheng D, Cheng X. Fructose‑1,6‑bisphosphatase‑1 decrease may promote carcinogenesis and chemoresistance in cervical cancer. Mol Med Rep 2017; 16:8563-8571. [PMID: 28990097 DOI: 10.3892/mmr.2017.7665] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Accepted: 09/05/2017] [Indexed: 11/06/2022] Open
Abstract
Fructose-1,6-bisphosphatase-1 (FBP1), a gluconeogenesis rate-limiting enzyme expressed in various tissues, is important in the carcinogenesis of various cancers. To evaluate the association of FBP1 expression and carcinogenesis and chemoresistance in cervical cancer, the present study analyzed 140 patients of squamous cell carcinoma of cervical cancer (CSCC) who had adjuvant concurrent chemoradiation therapy following radical surgery. By detecting FBP1 protein expression in paraffin‑embedded tumor tissues through immunohistochemistry, it was observed that 50% of the cases had a low expression of FBP1, which was associated with a shorter overall survival time (P=0.011). In addition, FBP1 mRNA level was downregulated in tumor tissues, compared with cervical normal tissues. Among the tumor‑associated prognostic factors, loss of FBP1 expression (χ2‑test, P=0.025) was significantly associated with the tumor recurrence and greater tumor stage of cervical cancer patients (2‑test, P<0.0001). In 3‑(4,5)‑dimethylthiahiazo(‑z‑y1)-3,5-diphenytetrazoliumromide (MTT) assay of primary tumor cells, the median in vitro inhibition rate of cisplatin, carboplatin, nedaplatin, and oxaliplatin was 62, 47, 58 and 52%, respectively. Although there was no significant association between FBP1 expression and in vitro tumor inhibition rates of primary tumor cells, overexpression of FBP1 markedly suppressed carcinogenesis and restored the chemosensitivity to cisplatin in cervical cancer cell lines of HeLa and CaSki. Overall, decreased levels of FBP1 may be used as a predictor for poor prognosis of cervical cancer patients, however the mechanism requires further investigation.
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Affiliation(s)
- Haoran Li
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
| | - Mengjiao Li
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
| | - Yangyang Pang
- Institute of Urology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, Gansu 730000, P.R. China
| | - Fei Liu
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
| | - Dong Sheng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
| | - Xi Cheng
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
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27
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Avallone G, Pellegrino V, Roccabianca P, Lepri E, Crippa L, Beha G, De Tolla L, Sarli G. Tyrosine Kinase Receptor Expression in Canine Liposarcoma. Vet Pathol 2016; 54:212-217. [DOI: 10.1177/0300985816671379] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor–β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP. Immunohistochemical labeling was categorized as high or low expression and compared with the mitotic count and MIB-1–based proliferation index. Fifty canine LPs were examined, classified, and graded. Fourteen cases were classified as well differentiated, 7 as myxoid, 25 as pleomorphic, and 4 as dedifferentiated. Seventeen cases were grade 1, 26 were grade 2, and 7 were grade 3. A high expression of FGF2, FGFR1, PDGFB, and PDGFRβ was identified in 62% (31/50), 68% (34/50), 81.6% (40/49), and 70.8% (34/48) of the cases, respectively. c-kit was expressed in 12.5% (6/48) of the cases. Mitotic count negatively correlated with FGF2 ( R = –0.41; P < .01), being lower in cases with high FGF2 expression, and positively correlated with PDGFRβ ( R = 0.33; P < .01), being higher in cases with high PDGFRβ expression. No other statistically significant correlations were identified. These results suggest that the PDGFRβ-mediated pathway may have a role in the progression of canine LP and may thus represent a promising target for adjuvant cancer therapies.
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Affiliation(s)
- G. Avallone
- Department of Veterinary Medical Sciences (DIMEVET), University di Bologna, Ozzano dell’Emilia, Italy
| | - V. Pellegrino
- Department of Veterinary Medical Sciences (DIMEVET), University di Bologna, Ozzano dell’Emilia, Italy
| | - P. Roccabianca
- Department of Veterinary Medicine (DIMEVET), University of Milan, Milan, Italy
| | - E. Lepri
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy
| | | | - G. Beha
- Department of Veterinary Medical Sciences (DIMEVET), University di Bologna, Ozzano dell’Emilia, Italy
| | - L. De Tolla
- Department of Pathology, School of Medicine, University of Maryland, Baltimore, MD, USA
| | - G. Sarli
- Department of Veterinary Medical Sciences (DIMEVET), University di Bologna, Ozzano dell’Emilia, Italy
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Horng HC, Wen KC, Wang PH, Chen YJ, Yen MS, Ng HT. Uterine sarcoma Part II-Uterine endometrial stromal sarcoma: The TAG systematic review. Taiwan J Obstet Gynecol 2016; 55:472-479. [PMID: 27590366 DOI: 10.1016/j.tjog.2016.04.034] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2016] [Indexed: 12/16/2022] Open
Abstract
Endometrial stromal tumors are rare uterine tumors (<1%). Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and uterine undifferentiated sarcoma (UUS). This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B) gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS). Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors.
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Affiliation(s)
- Huann-Cheng Horng
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Kuo-Chang Wen
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Peng-Hui Wang
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
| | - Yi-Jen Chen
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Shyen Yen
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Heung-Tat Ng
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Foundation of Female Cancer, Taipei, Taiwan
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29
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Hodge JC, Bedroske PP, Pearce KE, Sukov WR. Molecular Cytogenetic Analysis of JAZF1, PHF1, and YWHAE in Endometrial Stromal Tumors: Discovery of Genetic Complexity by Fluorescence in Situ Hybridization. J Mol Diagn 2016; 18:516-26. [PMID: 27154512 DOI: 10.1016/j.jmoldx.2016.02.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 11/28/2015] [Accepted: 02/03/2016] [Indexed: 12/22/2022] Open
Abstract
Diagnosis of endometrial stromal tumors (ESTs) can be challenging, particularly endometrial stromal sarcomas (ESSs) because of variable histologic appearance, long latency to recurrence, frequent metastases with unknown primary, and overlap with endometrial stromal nodules and undifferentiated uterine sarcomas. To enhance EST diagnosis, a break-apart strategy fluorescence in situ hybridization panel to detect JAZF1, PHF1, and YWHAE rearrangements was applied to a cohort of primary or metastatic endometrial stromal nodules, ESSs, or undifferentiated uterine sarcomas (36 cases for JAZF1, 24 of which were also assessed for PHF1 and YWHAE), 24 myometrium/endometrium controls, and 37 non-ESTs in the differential diagnosis. JAZF1 was the most frequently altered gene and occurred in all EST types, JAZF1 and/or PHF1 were mutually exclusive from YWHAE involvement, and uterine and extrauterine ESTs have a shared pathogenesis. We further defined frequency of these rearrangements and provided a resource demonstrating the signal complexity that can manifest when evaluating JAZF1. Rearrangement of JAZF1 occurred in 47% of ESTs, most (70%) of which had atypical patterns representing multiple structural alterations and/or more than one clone. YWHAE and PHF1 rearrangements each occurred in 8% of ESTs. An exceptional case was an ESS without JAZF1 or MEAF6 disruption that further disputes correlation of PHF1 involvement with the sex cord-like variant. These results expand our understanding of the genetic heterogeneity that defines ESTs.
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Affiliation(s)
- Jennelle C Hodge
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
| | - Patrick P Bedroske
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Kathryn E Pearce
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - William R Sukov
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
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30
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Denschlag D, Thiel FC, Ackermann S, Harter P, Juhasz-Boess I, Mallmann P, Strauss HG, Ulrich U, Horn LC, Schmidt D, Vordermark D, Vogl T, Reichardt P, Gaß P, Gebhardt M, Beckmann MW. Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015). Geburtshilfe Frauenheilkd 2015; 75:1028-1042. [PMID: 26640293 DOI: 10.1055/s-0035-1558120] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Due to their rarity and their heterogeneous histopathology uterine sarcomas remain challenging tumors to manage and need a multidisciplinary approach. To our knowledge so far there is no evidence-based guideline on the appropiate management of these heterogeneous tumors. Methods: This S2k-guideline is the work of an representative committee of experts from a variety of different professions who were commissioned by the DGGG to carry out a systematic literature review of uterine sarcoma. Members of the participating scientific societies developed a structured consensus in a formal procedure. Recommendations: 1. The incidence and histopathologic classification of uterine sarcoma. 2. The clinical manifestations, diagnosis and staging of uterine sarcoma. 3. The management of leiomyosarcoma. 4. The management of endometrial stromal sarcoma and undifferentiated uterine sarcoma. 5. The management of adenosarcoma as well as carcinosarcomas. 6. The management of morcellated uterine sarcoma.
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Affiliation(s)
- D Denschlag
- Frauenklinik, Hochtaunuskliniken Bad Homburg, Bad Homburg
| | - F C Thiel
- Frauenklinik, Alb Fils Kliniken, Göppingen
| | | | - P Harter
- Klinik für Gynäkologie und Gynäkologische Onkologie, Klinikum Essen Mitte, Essen
| | - I Juhasz-Boess
- Klinik für Gynäkologie, Geburtshilfe und Reproduktionsmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar
| | - P Mallmann
- Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Köln, Cologne
| | - H-G Strauss
- Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Halle, Halle/Saale
| | - U Ulrich
- Klinik für Gynäkologie und Geburtshilfe, Martin-Luther-Krankenhaus Berlin, Paul Gerhardt Diakonie, Berlin
| | - L-C Horn
- Abteilung für Mamma-, Urogenital, und Perinatalpathologie, Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig
| | - D Schmidt
- Institut für Pathologie Mannheim, Mannheim
| | - D Vordermark
- Universitätsklinik und Poliklinik für Strahlentherapie, Universitätsklinikum Halle, Halle/Saale
| | - T Vogl
- Institut für diagnostische und interventionelle Radiologie, Universitätsklinikum Frankfurt, Frankfurt/Main
| | - P Reichardt
- Klinik für interdisziplinäre Onkologie, Helios Kliniken Berlin-Buch, Berlin
| | - P Gaß
- Frauenklinik, Universitätsklinikum Erlangen, Erlangen
| | - M Gebhardt
- Frauenselbsthilfe nach Krebs e. V., Erlangen
| | - M W Beckmann
- Frauenklinik, Universitätsklinikum Erlangen, Erlangen
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Yamaguchi M, Erdenebaatar C, Saito F, Motohara T, Miyahara Y, Tashiro H, Katabuchi H. Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma. Int J Gynecol Cancer 2015; 25:1645-51. [PMID: 26495759 DOI: 10.1097/igc.0000000000000557] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND There has been no consensus on the indications for the treatment of advanced low-grade endometrial stromal sarcoma (LGESS), and the possible effects of hormonal treatment including progestins and aromatase inhibitors have been reported. The aim of this study was to investigate the efficacy of aromatase inhibitor therapy with letrozole for patients with residual or recurrent LGESS. METHODS We retrospectively reviewed the clinical response of patients with advanced LGESS who had been treated with letrozole. We also analyzed the adverse effects after the administration of letrozole. The expression levels of estrogen receptor and aromatase in the tumors were immunohistochemically examined. RESULTS In 5 patients who had been treated for unresectable LGESS lesions after initial or repeat surgical procedures, residual lesions in 3 patients and recurrence lesions in 2 patients were the indications for hormonal therapy with letrozole. The median duration of letrozole exposure at retrospective analysis was 53 (10-96) months. The clinical outcomes were classified as complete response in 2 patients, partial response in 1 patient, and stable disease in 2 patients. Myalgias, hot flashes, and arthralgias were not observed during the follow-up period in any patients. The median serum levels of estradiol were <5.0 (cutoff value, <0.5-11.8) pg/mL. The median age-matched bone mineral densities were 92% (79%-123%). The LGESS tissues in all 5 patients were positive for estrogen receptor and aromatase expression. CONCLUSIONS Letrozole as well as progestins could be the first choice of treatment for patients with recurrent or residual LGESS, which is difficult to resect surgically because of its efficacy and minimal adverse effects.
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Affiliation(s)
- Munekage Yamaguchi
- *Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; †Department of Obstetrics and Gynecology, Kumamoto General Hospital, Japan Community Health care Organization, Yatsushiro, Japan; and ‡Department of Mother-Child Nursing, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
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Potential Therapeutic Targets in Uterine Sarcomas. Sarcoma 2015; 2015:243298. [PMID: 26576131 PMCID: PMC4632006 DOI: 10.1155/2015/243298] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 09/30/2015] [Indexed: 12/30/2022] Open
Abstract
Uterine sarcomas are rare tumors accounting for 3,4% of all uterine cancers. Even after radical hysterectomy, most patients relapse or present with distant metastases. The very limited clinical benefit of adjuvant cytotoxic treatments is reflected by high mortality rates, emphasizing the need for new treatment strategies. This review summarizes rising potential targets in four distinct subtypes of uterine sarcomas: leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Based on clinical reports, promising approaches for uterine leiomyosarcoma patients include inhibition of VEGF and mTOR signaling, preferably in combination with other targeted or cytotoxic compounds. Currently, the only targeted therapy approved in leiomyosarcoma patients is pazopanib, a multitargeted inhibitor blocking VEGFR, PDGFR, FGFR, and c-KIT. Additionally, preclinical evidence suggests effect of the inhibition of histone deacetylases, tyrosine kinase receptors, and the mitotic checkpoint protein aurora kinase A. In low-grade endometrial stromal sarcomas, antihormonal therapies including aromatase inhibitors and progestins have proven activity. Other potential targets are PDGFR, VEGFR, and histone deacetylases. In high-grade ESS that carry the YWHAE/FAM22A/B fusion gene, the generated 14-3-3 oncoprotein is a putative target, next to c-KIT and the Wnt pathway. The observation of heterogeneity within uterine sarcoma subtypes warrants a personalized treatment approach.
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Zhou J, Zheng H, Wu SG, He ZY, Li FY, Su GQ, Sun JY. Influence of different treatment modalities on survival of patients with low-grade endometrial stromal sarcoma: A retrospective cohort study. Int J Surg 2015; 23:147-51. [PMID: 26449652 DOI: 10.1016/j.ijsu.2015.09.072] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 09/28/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND To assess the efficacy of different treatment modalities on the outcome of patients with low-grade endometrial stromal sarcoma (LG-ESS). METHODS Patients with LG-ESS who received hysterectomy from March 1991 to December 2013 were retrospectively analyzed. The associations between clinicopathologic variables and disease free survival (DFS) were evaluated. RESULTS One hundred and fourteen patients met the eligibility requirements. All patients received hysterectomy as the main treatment, 17.5% (20/114) of patients received ovarian preservation, and 62.3% (71/114) of patients received lymphadenectomy. Fifty-six patients received chemotherapy, 36 patients received radiotherapy, and 11 patients received endocrine therapy. The median follow-up duration was 40 months. The 5-year and 10-year DFS rates were 91.8% and 77.4%, respectively. The 5-year and 10-year overall survival rates were 96.7% and 96.7%, respectively. Univariate analyses showed that there were no risk factors associated with DFS. Lymphadenectomy, lymph node status, ovarian preservation, chemotherapy, radiotherapy, and endocrine therapy had no significant effect on DFS. CONCLUSIONS Hysterectomy has been the mainstay of treatment for LG-ESS. The optimal treatment strategy in LG-ESS remains to be determined.
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Affiliation(s)
- Juan Zhou
- Xiamen Cancer Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China
| | - Hua Zheng
- Xiamen Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China
| | - San-Gang Wu
- Xiamen Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China
| | - Zhen-Yu He
- Sun Yat-sen University Cancer Center, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| | - Feng-Yan Li
- Sun Yat-sen University Cancer Center, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| | - Guo-Qiang Su
- Department of Gastrointestinal Surgery Ward 3 Areas of Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
| | - Jia-Yuan Sun
- Sun Yat-sen University Cancer Center, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China.
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Laurelli G, Falcone F, Scaffa C, Messalli EM, Del Giudice M, Losito S, Greggi S. Fertility-sparing management of low-grade endometrial stromal sarcoma: analysis of an institutional series and review of the literature. Eur J Obstet Gynecol Reprod Biol 2015; 195:61-66. [PMID: 26476800 DOI: 10.1016/j.ejogrb.2015.09.041] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Revised: 09/20/2015] [Accepted: 09/28/2015] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Low-grade endometrial stromal sarcoma (LG-ESS) is a rare malignancy, often occurring before menopause. There is no consensus regarding its optimal management. Total hysterectomy and bilateral salpingo-oophorectomy precludes future fertility and may thus be undesirable by women wishing to maintain their reproductive potential. However, experience of fertility-sparing management in LG-ESS is very limited. In this paper, the disease outcome is presented in six young women with LG-ESS conservatively treated by combined hysteroscopic resection and hormonal therapy. STUDY DESIGN From October 2009 to February 2013, at the Gynecologic Oncology Department of the National Cancer Institute of Naples, six women, with early-stage LG-ESS aged 18-40 years who desired childbearing and/or retaining their fertility, were enrolled into a pilot study of fertility-sparing management. Diagnosis of LG-ESS was made on specimens from hysteroscopic resection performed on a presumed benign lesion. All patients were planned to be treated with adjuvant megestrol acetate for two years. Hormonal therapy was started within 6 weeks from the hysteroscopic resection, with orally megestrol acetate at 40mg daily, increasing gradually according to patient's tolerance to the recommended total dose of 160mg daily. RESULTS All patients were submitted to hysteroscopic resection in a one-step procedure. Five patients started megestrol acetate within 6 weeks from the hysteroscopic resection (one patient did not start hormonal therapy because of early pregnancy after the hysteroscopic resection). Hormonal therapy was well tolerated; one patient stopped megestrol acetate after 12 months because of self-supporting strong desire to conceive; the other four patients regularly completed the hormonal therapy. To date, all patients show no evidence of disease. CONCLUSIONS Although fertility-sparing management is not the current standard of care for young women with early-stage LG-ESS, our preliminary data are promising. Larger series with a longer follow-up are needed to further assess safety and efficacy of combined hysteroscopic resection and hormonal therapy.
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Affiliation(s)
- Giuseppe Laurelli
- Gynecologic Oncology Surgery, Istituto Nazionale Tumori "Fondazione G. Pascale" IRCCS, Naples, Italy
| | - Francesca Falcone
- Department of Woman, Child, and General and Specialized Surgery, Seconda Università degli Studi di Napoli, Naples, Italy
| | - Cono Scaffa
- Gynecologic Oncology Surgery, Istituto Nazionale Tumori "Fondazione G. Pascale" IRCCS, Naples, Italy
| | - Enrico M Messalli
- Department of Woman, Child, and General and Specialized Surgery, Seconda Università degli Studi di Napoli, Naples, Italy
| | - Maurizio Del Giudice
- Anesthesiology and Intensive Care, Istituto Nazionale Tumori "Fondazione G. Pascale" IRCCS, Naples, Italy
| | - Simona Losito
- Surgical Pathology, Istituto Nazionale Tumori "Fondazione G. Pascale" IRCCS, Naples, Italy
| | - Stefano Greggi
- Gynecologic Oncology Surgery, Istituto Nazionale Tumori "Fondazione G. Pascale" IRCCS, Naples, Italy.
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Harris SJ, Benson C, Jones RL. Current and advancing systemic treatment options for soft tissue sarcomas. Expert Opin Pharmacother 2015; 16:2023-37. [PMID: 26255951 DOI: 10.1517/14656566.2015.1074176] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Soft tissue sarcomas are a collection of rare malignancies, the treatment of which has evolved over time. Although cytotoxic chemotherapy remains the cornerstone of management of metastatic disease, many new treatments have been developed or show great promise in the treatment of soft tissue sarcoma. Research into the different underlying pathogenesis of individual subtypes has driven progress in treatment. This has allowed development of treatments targeted to specific subtypes of sarcoma. AREAS COVERED We provide a review of the current field of systemic therapy in soft tissue sarcoma. This is followed by an in-depth analysis of recent developments in treatment, as well as new treatments that are aimed at specific subtypes of sarcoma, and the biological rationale behind these therapies. We also look in detail at the promising new agents currently in development. EXPERT OPINION Much progression has been made in treatment of soft tissue sarcomas with multiple exciting new treatments in development. However outcomes in general remain poor. Further research into the underlying pathogenesis of soft tissue sarcomas may help deliver more effective systemic therapies. Increased collaboration between basic science, translational and clinical investigators is required at national and international levels to maximise progress.
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Affiliation(s)
- Samuel J Harris
- The Royal Marsden NHS Foundation Trust , Sarcoma Unit , Fulham Road, London, SW3 6JJ , UK
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Avallone G, Stefanello D, Boracchi P, Ferrari R, Gelain ME, Turin L, Tresoldi E, Roccabianca P. Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors. Vet Pathol 2015; 52:1034-40. [PMID: 25795373 DOI: 10.1177/0300985815575050] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Canine perivascular wall tumors (PWTs) are a group of subcutaneous soft tissue sarcomas developing from vascular mural cells. Mural cells are involved in angiogenesis through a complex crosstalk with endothelial cells mediated by several growth factors and their receptors. The evaluation of their expression may have relevance since they may represent a therapeutic target in the control of canine PWTs. The expression of vascular endothelial growth factor (VEGF) and receptors VEGFR-I/II, basic fibroblast growth factor (bFGF) and receptor Flg, platelet-derived growth factor B (PDGFB) and receptor PDGFRβ, transforming growth factor β1 (TGFβ1) and receptors TGFβR-I/II, and cyclooxygenase 2 (COX2) was evaluated on frozen sections of 40 PWTs by immunohistochemistry and semiquantitatively scored to identify their potential role in PWT development. Statistical analysis was performed to analyze possible correlations between Ki67 labeling index and the expression of each molecule. Proteins of the VEGF-, PDGFB-, and bFGF-mediated pathways were highly expressed in 27 (67.5%), 30 (75%), and 19 (47.5%) of 40 PWTs, respectively. Proteins of the TGFβ1- and COX2-mediated pathways were highly expressed in 4 (10%) and 14 (35%) of 40 cases. Statistical analysis identified an association between VEGF and VEGFR-I/II (P = .015 and .003, respectively), bFGF and Flg (P = .038), bFGF and PDGFRβ (P = .003), and between TGFβ1 and COX2 (P = .006). These findings were consistent with the mechanisms that have been reported to play a role in angiogenesis and in tumor development. No association with Ki67 labeling index was found. VEGF-, PDGFB-, and bFGF-mediated pathways seem to have a key role in PWT development and growth. Blockade of tyrosine kinase receptors after surgery could represent a promising therapy with the aim to reduce the PWT relapse rate and prolong the time to relapse.
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Affiliation(s)
- G Avallone
- Department of Veterinary Medical Sciences (DIMEVET), Università di Bologna, Ozzano dell'Emilia, Milano, Italy
| | - D Stefanello
- Dipartimento di scienze veterinarie e sanità pubblica (DIVET), Università degli studi di Milano, Milano, Italy
| | - P Boracchi
- Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Biometry and Epidemiology GA Maccacaro, Università degli Studi di Milano, Milano, Italy
| | - R Ferrari
- Dipartimento di scienze veterinarie e sanità pubblica (DIVET), Università degli studi di Milano, Milano, Italy
| | - M E Gelain
- Dipartimento di Biomedicina Comparata e Alimentazione, Università degli Studi di Padova, Agripolis-Legnaro (PD), Italy
| | - L Turin
- Dipartimento di scienze veterinarie e sanità pubblica (DIVET), Università degli studi di Milano, Milano, Italy
| | - E Tresoldi
- Dipartimento di scienze veterinarie e sanità pubblica (DIVET), Università degli studi di Milano, Milano, Italy
| | - P Roccabianca
- Dipartimento di scienze veterinarie e sanità pubblica (DIVET), Università degli studi di Milano, Milano, Italy
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REV3L, a promising target in regulating the chemosensitivity of cervical cancer cells. PLoS One 2015; 10:e0120334. [PMID: 25781640 PMCID: PMC4364373 DOI: 10.1371/journal.pone.0120334] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 01/29/2015] [Indexed: 12/14/2022] Open
Abstract
REV3L, the catalytic subunit of DNA Polymerase ζ (Polζ), plays a significant role in the DNA damage tolerance mechanism of translesion synthesis (TLS). The role of REV3L in chemosensitivity of cervical cancer needs exploration. In the present study, we evaluated the expression of the Polζ protein in paraffin-embedded tissues using immunohistochemistry and found that the expression of Polζ in cervical cancer tissues was higher than that in normal tissues. We then established some cervical cancer cell lines with REV3L suppression or overexpression. Depletion of REV3L suppresses cell proliferation and colony formation of cervical cancer cells through G1 arrest, and REV3L promotes cell proliferation and colony formation of cervical cancer cells by promoting G1 phase to S phase transition. The suppression of REV3L expression enhanced the sensitivity of cervical cancer cells to cisplatin, and the overexpression of REV3L conferred resistance to cisplatin as evidenced by the alteration of apoptosis rates, and significantly expression level changes of anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia sequence 1 (Mcl-1) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax). Our data suggest that REV3L plays an important role in regulating cervical cancer cellular response to cisplatin, and thus targeting REV3L may be a promising way to alter chemosensitivity in cervical cancer patients.
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Thanopoulou E, Aleksic A, Thway K, Khabra K, Judson I. Hormonal treatments in metastatic endometrial stromal sarcomas: the 10-year experience of the sarcoma unit of Royal Marsden Hospital. Clin Sarcoma Res 2015; 5:8. [PMID: 25810898 PMCID: PMC4373094 DOI: 10.1186/s13569-015-0024-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 02/23/2015] [Indexed: 11/27/2022] Open
Abstract
Background Hormonal manipulation is sometimes recommended in the treatment of metastatic endometrial stromal sarcoma, but there are few data assessing the efficacy of endocrine therapies in this subtype of uterine sarcomas. Methods We performed a retrospective electronic medical record review of patients with metastatic ESS treated with a hormonal agent at Royal Marsden Hospital between 1999 and 2011. We assessed progression-free survival (PFS), objective response and toxicity profile among patients with measurable disease. Results Thirteen patients with metastatic ESS were treated with hormonal therapies. Hormone receptor status (estrogen and progesterone receptors) was assessed in 9 out of 13 patients and in all of them it was moderately to strongly positive. Aromatase inhibitors (AIs) were prescribed as first endocrine line in 11/13 patients and progestins in the remainder, while in 2nd line treatment AIs were prescribed in 7/10 patients, followed by progestins and GnRH analogues. Median PFS for 1stline was 4.0 years (95% CI: 2.4 – 5.5 years) with 5-year progression-free rate of 30.8% (95% CI: 5.7 – 55.9%), both of which reflect the indolent natural history of ESS. Best objective response was partial response (PR) in 6/13 patients (46.2%; 95% CI: 19.2 – 74.9) and clinical benefit rate (defined as complete response + PR + stable disease ≥6 months) was 92.4% (95% CI: 64.0 – 99.8%; 12/13 patients). Median PFS for 2nd line was 3.0 years (95% CI: 2.0 – 4.1 years) with 2-year progression-free rate of 88.9% (95% CI: 68.3 – 100.0). Conclusions In this cohort of metastatic ESS patients, 1st line endocrine treatment achieved objective response in 46.2% of them and clinical benefit in 92.4%. Tamoxifen and hormone replacement therapy should not be prescribed in patients with ESS due to their detrimental effects. Until more solid data are available, a reasonable recommendation would be that 1st line treatment with an endocrine treatment, preferably with an AI. Moreover, in view of the positive outcomes of our patients that received 2nd/3rdline endocrine treatments, all available hormonal options should be used in sequence in the management of ESS.
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Affiliation(s)
- Eirini Thanopoulou
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, Chelsea, London SW3 6JJ UK
| | - Aleksandar Aleksic
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, Chelsea, London SW3 6JJ UK
| | - Khin Thway
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, Chelsea, London SW3 6JJ UK
| | - Komel Khabra
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, Chelsea, London SW3 6JJ UK
| | - Ian Judson
- Sarcoma Unit, Royal Marsden NHS Foundation Trust, Chelsea, London SW3 6JJ UK
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Zaza KJ, Arafah MA, Al-Badawi IA. Vulvar extrauterine endometrial stromal sarcoma: A case report and literature review. Hematol Oncol Stem Cell Ther 2015; 8:125-9. [PMID: 25585306 DOI: 10.1016/j.hemonc.2014.12.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 11/19/2014] [Accepted: 12/09/2014] [Indexed: 11/30/2022] Open
Abstract
Endometrial stromal sarcoma (ESS) is an extremely rare neoplasm accounting for only 0.2% of all uterine malignancies and for 15-26% of primary uterine sarcomas. The annual incidence of ESS is 1-2 per million women. Herein, to the best of our knowledge, we present the first reported case of ESS of the vulva in a 50-year-old female presenting with per vaginal spotting over a period of three months. Her past surgical history included a subtotal hysterectomy and left salpingo-oophorectomy for uterine fibroids ten years previously. On examination, a 3.5×3×2 cm cystic mass was found in the right labia majora. The mass was excised and the diagnosis of endometrial stromal sarcoma was made. Subsequent metastatic workup was negative and the patient was started on megestrol acetate. She has remained disease free with no signs or symptoms of recurrent or advanced disease for 28 months.
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Affiliation(s)
- Khaled J Zaza
- College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia.
| | - Maria A Arafah
- Department of Pathology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia.
| | - Ismail A Al-Badawi
- Department of Obstetrics and Gynecology, King Faisal Specialist Hospital and Research Centre (KFSH & RC), P.O. Box 3354, Riyadh 11211, Saudi Arabia.
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He L, Li JD, Xiong Y, Huang X, Huang L, Lin JX, Zhou Y, Zheng M. Clinicopathological and molecular markers associated with prognosis and treatment effectiveness of endometrial stromal sarcoma: a retrospective study in China. Arch Gynecol Obstet 2014; 289:383-91. [PMID: 23959089 PMCID: PMC3894427 DOI: 10.1007/s00404-013-2987-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2012] [Accepted: 07/26/2013] [Indexed: 11/11/2022]
Abstract
Purpose
To evaluate the clinicopathological and immunophenotypic characteristics of endometrial stromal sarcoma (ESS) in China. Methods and materials Seventy-two consecutive ESS cases treated between 1995 and 2009 were retrospectively reviewed. Results Sixty-three patients received surgical treatment. Forty-one patients underwent pelvic lymphadenectomy. In paraffin-embedded specimens, expression of the following molecular markers was detected: CD10 (27/36), vimentin (37/38), HHF35 (3/32), S-100 (0/25), desmin (2/29), CD117 (0/23), CD34 (2/24), alpha-inhibin (0/17), CK (1/34), CD99 (4/9), smooth muscle actin (5/25), EMA (0/7), estrogen receptor (13/16) and progesterone receptor (13/16). CD10 and vimentin were expressed more frequently in these specimens. Tumor classification, CD10 and surgical procedures were significantly associated with disease-free survival (DFS). Surgical procedures were significantly associated with overall survival (OS). Tumor stage (P = 0.024) and surgical procedure (P = 0.042) were found to be significant independent prognostic factors for DFS. No complete or partial response was observed among patients who received radiotherapy or chemotherapy. Conclusions Our results indicate that total hysterectomy with bilateral salpingo-oophorectomy followed by pelvic lymphadenectomy is associated with an improved treatment outcome. CD10-negative expression may contribute to the malignant characteristics and recurrence associated with ESS.
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Abstract
Endometrial stromal tumors are rare uterine mesenchymal neoplasms that have intrigued pathologists for years, not only because they commonly pose diagnostic dilemmas, but also because the classification and pathogenesis of these tumors has been widely debated. The current World Health Organization recognizes 4 categories of endometrial stromal tumor: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). uterine sarcoma. These categories are defined by the presence of distinct translocations as well as tumor morphology and prognosis. Specifically, the JAZF1-SUZ12 (formerly JAZF1-JJAZ1) fusion identifies a large proportion of ESN and LG-ESSs, whereas the YWHAE-FAM22 translocation identifies HG-ESSs. The latter tumors appear to have a prognosis intermediate between LG-ESS and UUS, which exhibits no specific translocation pattern. This review (1) presents the clinicopathologic features of endometrial stromal tumors; (2) discusses their immunophenotype; and (3) highlights the recent advances in molecular genetics which explain their pathogenesis and lend support for a new classification system.
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Cade TJ, Quinn MA, Rome RM, Polyakov A. Prognostic significance of steroid receptor positivity and adjuvant progestogen use in endometrial stromal sarcoma. Aust N Z J Obstet Gynaecol 2014; 54:453-6. [DOI: 10.1111/ajo.12245] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2014] [Accepted: 07/14/2014] [Indexed: 11/28/2022]
Affiliation(s)
- Thomas J. Cade
- Department of Obstetrics and Gynaecology; Royal Women's Hospital; Parkville Victoria Australia
| | - Michael A. Quinn
- Department of Obstetrics and Gynaecology; Royal Women's Hospital; Parkville Victoria Australia
- Department of Obstetrics and Gynaecology; University of Melbourne; Parkville Victoria Australia
| | - Robert M. Rome
- Department of Obstetrics and Gynaecology; Royal Women's Hospital; Parkville Victoria Australia
- Obstetrics and Gynaecology Institute; Epworth Freemasons Hospital; Melbourne Victoria Australia
| | - Alexander Polyakov
- Department of Obstetrics and Gynaecology; Royal Women's Hospital; Parkville Victoria Australia
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Morimoto A, Tsubamoto H, Inoue K, Ikeda Y, Hirota S. Fatal case of multiple recurrences of endometrial stromal sarcoma after fertility-sparing management. J Obstet Gynaecol Res 2014; 41:162-6. [DOI: 10.1111/jog.12506] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Accepted: 05/21/2014] [Indexed: 11/26/2022]
Affiliation(s)
- Atsushi Morimoto
- Department of Obstetrics and Gynecology; Hyogo College of Medicine; Nishinomiya Hyogo Japan
| | - Hiroshi Tsubamoto
- Department of Obstetrics and Gynecology; Hyogo College of Medicine; Nishinomiya Hyogo Japan
| | - Kayo Inoue
- Department of Obstetrics and Gynecology; Hyogo College of Medicine; Nishinomiya Hyogo Japan
- Department of Obstetrics and Gynecology; Meiwa General Hospital; Nishinomiya Hyogo Japan
| | - Yuuki Ikeda
- Department of Obstetrics and Gynecology; Hyogo College of Medicine; Nishinomiya Hyogo Japan
| | - Seiichi Hirota
- Department of Surgical Pathology; Hyogo College of Medicine; Nishinomiya Hyogo Japan
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Reversion of Hormone Treatment Resistance with the Addition of an mTOR Inhibitor in Endometrial Stromal Sarcoma. Case Rep Med 2014; 2014:612496. [PMID: 25104960 PMCID: PMC4109292 DOI: 10.1155/2014/612496] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 06/30/2014] [Indexed: 01/08/2023] Open
Abstract
Background. Endometrial stromal sarcomas (ESS) are a subtype of gynaecological sarcomas characterized by the overexpression of hormone receptors. Hormone treatment is widely used in ESS but primary or acquired resistance is common. The mammalian target of rapamycin (mTOR) pathway has been suggested to play a key role in the mechanisms of hormone resistance. Recent studies in breast and prostate cancer demonstrate that this resistance can be reversed with the addition of an mTOR inhibitor. This phenomenon has never been reported in ESS. Methods. We report the outcome of one patient with pretreated, progressing low grade metastatic ESS treated with medroxyprogesterone acetate in combination with the mTOR inhibitor sirolimus. Results. Partial response was achieved following the addition of sirolimus to the hormone treatment. Response has been maintained for more than 2 years with minimal toxicity and treatment is ongoing. Conclusion. This case suggests that the resistance to the hormone manipulation in ESS can be reversed by the addition of an mTOR pathway inhibitor. This observation is highly encouraging and deserves further investigation.
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El-Khalfaoui K, du Bois A, Heitz F, Kurzeder C, Sehouli J, Harter P. Current and future options in the management and treatment of uterine sarcoma. Ther Adv Med Oncol 2014; 6:21-8. [PMID: 24381658 DOI: 10.1177/1758834013513314] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Uterine sarcomas are rare aggressive mesenchymal tumours with limited prognosis. They encompass various histological subtypes such leiomyosarcoma, endometrial stromal sarcoma and undifferentiated sarcomas with different surgical and medical strategies. Current evidence of surgery, adjuvant and palliative therapy is reported.
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Affiliation(s)
- Khalid El-Khalfaoui
- Department of Gynecology & Gynecologic Oncology, Kliniken Essen Mitte (KEM), Evang. Huyssens-Stiftung/Knappschaft GmbH, Henricistr. 92, 45136 Essen, Germany
| | - Andreas du Bois
- Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen Germany
| | - Florian Heitz
- Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen Germany
| | - Christian Kurzeder
- Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen Germany
| | - Jalid Sehouli
- Department of Gynecology, Charité Medical University of Berlin, Berlin, Germany
| | - Philipp Harter
- Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen Germany
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Abstract
Immunohistochemistry may be helpful in the diagnosis of mesenchymal uterine tumors. This article reviews the immunoreactions used most frequently in the diagnosis of uterine smooth muscle tumors, endometrial stromal tumors, undifferentiated endometrial sarcomas, UTROSCTs, PEComas, adenomyomas, adenosarcomas and carcinosarcomas.
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Affiliation(s)
- Emanuela D'Angelo
- Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Floor C-2, Sant Quintí, 87-89, 08041 Barcelona, Spain.
| | - Jaime Prat
- Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Floor C-2, Sant Quintí, 87-89, 08041 Barcelona, Spain.
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Harter P, El-Khalfaoui K, Heitz F, du Bois A. Operative and Conservative Treatment of Uterine Sarcomas. Geburtshilfe Frauenheilkd 2014; 74:267-270. [PMID: 24882876 DOI: 10.1055/s-0034-1368204] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Revised: 02/13/2014] [Accepted: 02/14/2014] [Indexed: 01/01/2023] Open
Abstract
Uterine sarcomas are rare, aggressive mesenchymal tumours with a relatively poor prognosis. The term comprises various histological subtypes, such as leiomyosarcoma, endometrial stromal sarcomas as well as undifferentiated uterine sarcomas, which require different operative and systemic/radiation therapy strategies accordingly. The evidence on operative, adjuvant and palliative treatment currently available is presented here.
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Affiliation(s)
- P Harter
- Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen
| | - K El-Khalfaoui
- Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen
| | - F Heitz
- Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen
| | - A du Bois
- Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen
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Linch M, Miah AB, Thway K, Judson IR, Benson C. Systemic treatment of soft-tissue sarcoma-gold standard and novel therapies. Nat Rev Clin Oncol 2014; 11:187-202. [PMID: 24642677 DOI: 10.1038/nrclinonc.2014.26] [Citation(s) in RCA: 166] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Soft-tissue sarcoma (STS) is a rare and heterogeneous group of tumours that comprise approximately 1% of all adult cancers, and encompass over 50 different subtypes. These tumours exhibit a wide range of differing behaviours and underlying molecular pathologies, and can arise anywhere in the body. Surgical resection is critical to the management of locoregional disease. In the locally advanced or metastatic disease settings, systemic therapy has an important role in the multidisciplinary management of sarcoma. Cytotoxic therapy that usually consists of doxorubicin and ifosfamide has been the mainstay of treatment for many years. However recent advances in molecular pathogenesis, the development of novel targeted therapies, changes in clinical trial design and increased international collaboration have led to the development of histology-driven therapy. Furthermore, genomic profiling has highlighted that some STS are driven by translocation, mutation or amplification and others have more complex and chaotic karyotypes. In this Review, we aim to describe the current gold standard treatment for specific STS subtypes as well as outline future promising therapies in the pipeline.
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Affiliation(s)
- Mark Linch
- Sarcoma Unit, Department of Medical Oncology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | - Aisha B Miah
- Department of Clinical Oncology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | - Khin Thway
- Department of Histopathology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | - Ian R Judson
- Sarcoma Unit, Department of Medical Oncology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | - Charlotte Benson
- Sarcoma Unit, Department of Medical Oncology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
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49
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Thanopoulou E, Judson I. Hormonal therapy in gynecological sarcomas. Expert Rev Anticancer Ther 2014; 12:885-94. [DOI: 10.1586/era.12.74] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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50
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Yoon A, Park JY, Park JY, Lee YY, Kim TJ, Choi CH, Bae DS, Kim BG, Lee JW, Nam JH. Prognostic factors and outcomes in endometrial stromal sarcoma with the 2009 FIGO staging system: A multicenter review of 114 cases. Gynecol Oncol 2014; 132:70-5. [DOI: 10.1016/j.ygyno.2013.10.029] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Revised: 10/22/2013] [Accepted: 10/24/2013] [Indexed: 02/04/2023]
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