• DNA methylation
• cancer
• epigenetics
• inflammation
• oxidative stress

• Humans
• DNA Methylation
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/etiology
• Neoplasms/pathology
• Inflammation/genetics
• Inflammation/complications
• Inflammation/metabolism
• Oxidative Stress/genetics
• Chronic Disease
• Epigenesis, Genetic
• Animals

• Canterbury Medical Research Foundation and the Wellington Research Foundation: Research for Life

• Endometriosis
• estrogens
• iron
• malignant transformation
• ovarian cancers

• Endometriosis/complications
• Endometriosis/genetics
• Endometriosis/pathology
• Female
• Ovarian Neoplasms/etiology
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/pathology
• Cell Transformation, Neoplastic/pathology
• Iron Overload
• Estrogens
• Carcinoma, Endometrioid/complications
• Carcinoma, Endometrioid/pathology
• Tumor Microenvironment

• ARID1A
• KRAS
• PI3K/mTOR
• endometriosis
• endometriosis-associated cancer
• estrogen
• inflammation
• organoids
• ovarian cancer
• single-cell RNA sequencing

• Endometriosis/pathology
• Endometriosis/genetics
• Endometriosis/etiology
• Endometriosis/metabolism
• Humans
• Female
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/etiology
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/metabolism
• Mutation
• Animals

• 021220FD2951 Nazarbayev University
• 021220CRP1722 Nazarbayev University

• ARD1A
• cancer
• clear-cell carcinoma
• endometrioid adenocarcinoma
• endometriosis
• ovarian cancer

• atypical endometriosis
• endometriosis
• endometriosis and risk of malignancy
• endometriosis-associated ovarian cancer
• ultrasound and endometriosis

• endometriosis
• heme
• heme metabolism
• macrophage
• oxidative stress

• Endometriosis/metabolism
• Endometriosis/drug therapy
• Female
• Humans
• Heme/metabolism
• Heme Oxygenase-1/metabolism
• Animals
• Signal Transduction
• Macrophages/metabolism
• Macrophages/immunology
• Autophagy
• Cytokines/metabolism

• NSFC 82072872 82071624 81871143 National Natural Science Foundation of China
• JIF157602 Zhuoxue of Fudan University
• IDF157014/002 Original Personalized Research of Fudan University

• Endometriosis
• Endometriosis-associated ovarian cancers
• Immune response
• Immunotherapy
• Ovarian neoplasms

• EAOC
• endometriosis
• ovarian cancer

• Humans
• Endometriosis/genetics
• Endometriosis/metabolism
• Endometriosis/pathology
• Endometriosis/etiology
• Endometriosis/complications
• Female
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/etiology
• Ovarian Neoplasms/metabolism
• Tumor Microenvironment
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Genetic Predisposition to Disease
• Signal Transduction
• Clinical Relevance

• endometriosis endometrial carcinoma hypoxia immunohistochemistry ovarian carcinoma

• Female
• Humans
• Ki-67 Antigen
• Endometriosis
• Cadherins/metabolism
• Ovarian Neoplasms
• Carcinoma, Ovarian Epithelial

• carcinoma of unknown primary
• endometriosis
• endosalpingiosis
• ovarian carcinoma
• pathogenesis
• retroperitoneal carcinoma
• spontaneous regression
• vanishing cancer

• none Kameda Medical Center

• diet associations
• diet recommendations
• endometriosis
• gluten-free
• omega-3
• red meat

• ARID1A mutations
• PI3K/AKT/mTOR pathway
• endometriosis
• endometrium
• ovarian cancer

• Female
• Humans
• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• Endometriosis
• Ovarian Neoplasms
• TOR Serine-Threonine Kinases
• Phosphatidylinositol 3-Kinase
• Carcinoma

• ca125
• he4
• ca72-4
• ovarian endometriosis
• prognostic

• ARID1A
• HDAC6
• IL-10 and EAOC
• Macrophage polarization
• Vorinostat

• anti-metastasis
• apoptosis
• medicinal chemistry
• natural compounds
• ovarian cancer
• semi-synthetic compounds

• Female
• Humans
• Biological Products/chemistry
• Cell Proliferation
• Ovarian Neoplasms/drug therapy

• DNA methylation
• histological examination
• metaplasia
• ovarian endometrioma
• peritoneal endometriosis

• Japan Society for the Promotion of Science

• Breast cancer
• Endometrial cancer
• Endometriosis
• Meta-analysis
• Risk

• Female
• Humans
• Endometriosis/complications
• Endometriosis/epidemiology
• Breast Neoplasms/epidemiology
• Breast Neoplasms/complications
• Endometrial Neoplasms/epidemiology
• Case-Control Studies
• Odds Ratio

• Bioinformatic analysis
• Biomarker
• Cyst fluid
• Iron metabolism
• Ovarian endometriosis

• Biomarkers/analysis
• Biomarkers/blood
• Biomarkers/metabolism
• Cyst Fluid/chemistry
• Cyst Fluid/metabolism
• Endometriosis/blood
• Endometriosis/etiology
• Endometriosis/metabolism
• Female
• Ferritins/blood
• Ferritins/metabolism
• Humans
• Iron/analysis
• Iron/blood
• Iron/metabolism
• Ovarian Diseases/blood
• Ovarian Diseases/etiology
• Ovarian Diseases/metabolism
• Transferrin/analysis
• Transferrin/metabolism

Background: Endometriosis is a complex gynecologic disorder that has been associated with a higher risk of ovarian cancer. The purpose of this work is to determine to what extent a history of endometriosis is a risk factor for ovarian cancer in a Spanish population. Methods: A retrospective case–control study was conducted using de-identified data from the Spanish National Health System’s “Primary Care Clinical Database” and “Hospital Minimum Basic Data Set” for the period 2013–2017. Multiple logistics regression analysis was conducted to determine associations between ovarian cancer and endometriosis controlled by sociodemographic characteristics and comorbidities. Results: Data from 608,980 women were analyzed, with 4505 presenting ovarian cancer. Endometriosis patients were shown to have a 2.66-fold increased risk of ovarian cancer when compared to those who did not have endometriosis by controlling age and other relevant comorbidities. Conclusions: This case–control study based on clinical administrative data has found that a history of endometriosis is independently associated with an increased risk of ovarian cancer. More research is needed to determine if a history of endometriosis affects survival results in ovarian cancer patients.

• cancer stem cells
• cross talks
• epigenetics
• metabolism
• oncometabolites

• cancer microenvironment
• cancer stem cells

• Cell Differentiation
• Humans
• Inflammation/pathology
• Neoplasms/pathology
• Neoplastic Stem Cells/pathology
• Tumor Microenvironment

Clear cell carcinoma of abdominal wall is a very rare and aggressive disease. It is mostly related to malignant transformation of abdominal wall endometriosis. This paper provides a new case report and a literature review of primitive abdominal wall clear cell carcinoma.

A 45-year-old woman with a history of a two previous caesarian section presented to the outpatient department with a tumor mass evolving since 10 years in the lower right quadrant of her abdomen. Imaging studies revealed a voluminous subcutaneous mass developing at the expense of the anterior abdominal wall. Surgical resection of the mass was performed. Histopathological examination along with immunohistochemical analysis were consistent with clear cell carcinoma. Biopsies of the endometrium and ovaries were performed and were negative for malignancy. The patient underwent therefore a hysterectomy with bilateral salpingo-oophorectomy which did not reveal any disease. The diagnosis of primitive clear cell carcinoma of the abdominal wall was then confirmed.

Primitive clear cell carcinoma of the abdominal wall is an extremely rare form of cancer with usually poor prognosis. Clinicians must be aware of the possibility of malignancy of any swelling mass occurring near or within a caesarean section scar.

Reporting more such cases is still needed to further progress in the understanding of this malignancy in addition to the development of treatment strategies.

•

Clear cell carcinoma (CCC) occurring in the anterior abdominal wall is an extremely rare but aggressive tumor.

To compare the incidence and survival rates of primary ovarian clear cell carcinoma (OCCC) and ovarian serous carcinoma (OSC) from a nationwide collected database.

We extracted information of patients with primary OCCC and OSC from the Korea Central Cancer Registry recorded between 1999 and 2018, including age at diagnosis and the Surveillance, Epidemiology, and End Results summary stage. Age-standardized incidence rates (ASRs) and annual percent changes (APCs) were calculated. Baseline characteristics and overall survival (OS) were compared between the OCCC and OSC groups.

Overall, the incidence rate of primary OCCC increased markedly from 1999 (ASR, 0.16/100,000) to 2018 (0.76/100,000) (APC, 7.85%; P<0.0001). Patients with OCCC were significantly younger and had early-stage disease more frequently than those with OSC. Patients diagnosed with OCCC before the age of 50 showed better OS than those diagnosed after the age of 50 (P=0.0048). The 5-year OS of the OCCC group did not differ by study period [73.5% (1999–2008) vs. 75.4% (2009–2018), P=0.3187], whereas the 5-year OS of the OSC group improved from 54.4% to 58% (P=0.0003).

Our nationwide registry-based study demonstrated that the incidence of OCCC in Korea increased significantly from 1999 to 2018. Early-stage OCCC had a relatively good prognosis, but advanced-stage OCCC had a worse OS than advanced-stage OSC. Therefore, the development of optimal treatment strategies for OCCC is warranted.

• clear cell carcinoma
• histologic subtype
• incidence
• ovarian cancer
• serous carcinoma
• survival

• clinical epidemiology
• biomarkers of disease
• epigenomics
• tumor clustering
• gynecologic neoplasms

• Adenocarcinoma, Clear Cell/ethnology
• Adenocarcinoma, Clear Cell/genetics
• Adenocarcinoma, Clear Cell/pathology
• Adult
• Aged
• Aged, 80 and over
• Aneuploidy
• Class I Phosphatidylinositol 3-Kinases/genetics
• CpG Islands/genetics
• DNA Methylation
• DNA-Binding Proteins/genetics
• Disease Progression
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Middle Aged
• Mutation
• Neoplasm Staging
• Ovarian Neoplasms/ethnology
• Ovarian Neoplasms/genetics
• Ovarian Neoplasms/pathology
• Prognosis
• Transcription Factors/genetics
• Tumor Suppressor Protein p53/genetics

• P30 CA047904 NCI NIH HHS
• P30 CA008748 NCI NIH HHS
• P50 CA228991 NCI NIH HHS
• 15601 Cancer Research UK
• P30 CA015083 NCI NIH HHS
• R01 CA248288 NCI NIH HHS
• R21 CA222867 NCI NIH HHS
• 22905 Cancer Research UK
• P50 CA136393 NCI NIH HHS

To evaluate the clinical outcome of atypical endometriosis and its association with ovarian malignancy.

This retrospective study included patients diagnosed with atypical endometriosis between January 2001 and December 2017. All patients had received surgical treatment for ovarian tumor. The clinical characteristics and histopathological results of all patients were reviewed.

Atypical endometriosis was diagnosed in 101 patients. We analyzed 98 patients with a mean age of 34.8 years (range: 16–58 years). Ten patients (10.2%) had previously undergone endometriosis surgery more than once. In total, 12 (12.2%) patients had atypical endometriosis-associated ovarian malignancy—nine had carcinomas and three had borderline tumor. The tumors were pathologically classified as follows: five, clear cell carcinomas; two, endometrioid adenocarcinomas; one, mixed clear cell and endometrioid adenocarcinoma; one, seromucinous carcinoma; two, mucinous borderline tumors; and one, seromucinous borderline tumor.

Atypical endometriosis is most frequently associated with clear cell carcinoma and endometrioid adenocarcinoma. To identify the risk of ovarian malignancy and manage patients with endometriosis, diagnosing atypical endometriosis and recognizing its precancerous potential are important.

• Adenocarcinoma
• Atypical endometriosis
• Clear cell carcinoma
• Ovarian malignancy

• Abdominal wall endometriosis
• Diagnosis
• Epidemiology
• Malignant transformation
• Outcome
• Systematic review
• Treatment

• Abdominal Wall/diagnostic imaging
• Abdominal Wall/surgery
• Carcinoma, Endometrioid/pathology
• Cesarean Section/adverse effects
• Cicatrix/pathology
• Endometriosis/diagnosis
• Endometriosis/epidemiology
• Endometriosis/therapy
• Female
• Humans
• Pregnancy

• Endometriosis-associated cancers
• borderline ovarian cancer
• breast cancer
• cervical cancer
• clear cell ovarian cancer
• endometrioid
• endometrium
• invasive serous ovarian cancer
• transformation atypical endometriosis

• Deep infiltrating endometriosis
• Endometriosis-associated complex hyperplasia
• Endometriosis-associated endometrioid cancer
• Synchronous endometrial cancer
• Vaginal cancer originating from endometriosis

Background: Endometriosis is a benign estrogen-dependent gynecological disease involving components of the female genital tract (uterus, Fallopian tubes, ovaries, large, round, and utero-sacral ligaments) and intra- and extraperitoneal regions. Since the moment of its etiopathogeny has been identified, the intrinsic capacity of endometriosis malignant transformation has been hypothesized. Patients,Materials and Methods: Our study included a total number of 50 patients diagnosed with endometriosis (31 cases) and endometriosis-related ovarian carcinoma (EOC) (19 cases). A clinicopathological and immunohistochemical study directed towards the detection of atypical transition lesions and the similitudes in epithelial–mesenchymal transition (EMT) phenomenon [E-cadherin/β-catenin/cytokeratin 18 (CK18)], apoptosis [B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X (Bax)], and hormonal dynamics mirrored by the immunoexpression of estrogen receptor (ER) and progesterone receptor (PR) in endometriosis and EOC glands and stroma has been performed. Results: Our study showed a higher immunoexpression of CK18 and E-cadherin in endometriosis than in neoplastic counterparts, while β-catenin had a stronger immunoexpression in tumors compared with endometriotic areas, with statistically significant differences between the studied groups. Bcl-2/Bax higher rate in endometriosis had a statistically significant association to a more aggressive tumor behavior (p=0.020). ER immunoexpression was stronger in endometriosis, with less negative scores compared to EOC, while PR immunoexpression was stronger in endometriosis, with a lower percent of negative scores compared to EOC. PR immunostaining was correlated to ovarian location of endometriosis (p=0.004) and tumor grade of EOC (p=0.027). Stromal ER and PR immunoexpression has been significantly lower in endometriosis in comparison to tumor stroma (p=0.001) and PR stromal immunoexpression had been higher in more differentiated tumors compared to less differentiated types (p=0.005). Conclusions: Our study supports that endometriosis is a precursor of EOC by the identification and the coexistence of both lesions in the investigated cases, the identification of intermediate lesions, as well as the expression of EMT immunomarkers, along with apoptosis and steroid receptors immunoexpression.

Ovarian clear cell carcinomas (OCCCs) are resistant to conventional anti-cancer drugs; moreover, the prognoses of advanced or recurrent patients are extremely poor. OCCCs often arise from endometriosis associated with strong oxidative stress. Of note, the stress involved in OCCCs can be divided into the following two categories: (a) carcinogenesis from endometriosis to OCCC and (b) factors related to treatment after carcinogenesis. Antioxidants can reduce the risk of OCCC formation by quenching reactive oxygen species (ROS); however, the oxidant stress-tolerant properties assist in the survival of OCCC cells when the malignant transformation has already occurred. Moreover, the acquisition of oxidative stress resistance is also involved in the cancer stemness of OCCC. This review summarizes the recent advances in the process and prevention of carcinogenesis, the characteristic nature of tumors, and the treatment of post-refractory OCCCs, which are highly linked to oxidative stress. Although therapeutic approaches should still be improved against OCCCs, multi-combinatorial treatments including nucleic acid-based drugs directed to the transcriptional profile of each OCCC are expected to improve the outcomes of patients.

• antioxidant
• cancer stemness
• endometriosis
• ovarian clear cell carcinoma

Ovarian endometriosis is a frequent chronic gynecological disease with an uncertain evolution regarding its progression or association with ovarian malignant lesions. The present review summarized the histological aspects, gene expression and microRNA (miRNA/miR) alterations associated with ovarian endometriosis and cancer and their possible interaction. The endometriosis-ovarian cancer interaction has been proposed by certain researchers as a single entity. Histological results indicated that endometriosis has been in different circumstances coexisting with ovarian cancer, with reference to endometrioid and clear cell carcinoma. Endometriosis with moderate and severe atypia can influence cell proliferation and architecture, resulting in a possible malignant transformation. Gene expression analysis indicated that the pathologies of both endometriosis and ovarian cancer are characterized by genetic instability from a molecular point of view, as several important genetic mutations, including ARID1A, PI3KCA, PTEN, BRCA1, BRCA2, TP53 and KRAS genes, were identified. miRNA alterations have been implicated in the regulation of gene expression. Common dysregulated miRNAs, such as miR-331, miR-335, miR-891, miR-548, miR-124, miR-148, miR-215, miR-192, miR-337, miR-153, miR-155, miR-144, miR-221 and miR-3688 were extensively investigated in understanding endometriosis and ovarian cancer evolution. From a combined viewpoint including histological aspects, gene expression and miRNA alterations, it is reasonable to speculate that endometriosis is associated with ovarian cancer. Ovarian endometriosis lesions may present a risk for ovarian malignant lesions, which supports a model of endometriosis as a malignant precursor. However, the endometriosis-ovarian cancer association is not widely accepted in the literature and additional studies are required to validate this association.

• gene expression
• histology
• miRNAs
• ovarian cancer
• ovarian endometriosis

• -PCR
• Ovarian endometriosis
• ectopic
• eutopic
• nano LC–MS
• proteomes

• Annexin A5/metabolism
• Biomarkers/metabolism
• Case-Control Studies
• Endometriosis/metabolism
• Endometrium/metabolism
• Female
• Humans
• Intercellular Signaling Peptides and Proteins/metabolism
• Lumican/metabolism
• Ovarian Diseases/metabolism
• Proteome
• Transferrin/metabolism

Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 μm), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNFα stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.

• 12Z
• Kenzan
• biofabrication
• endometriosis
• scaffold-free
• spheroid

• ULITR001108 NCATS NIH HHS
• P30 CA125123 NCI NIH HHS

• biomarkers
• cytokines
• endometriosis
• ovarian neoplasms

• Angiogenesis
• Bevacizumab
• Experimental endometriosis
• VEGF

• Clear cell carcinoma
• Endometrioid adenocarcinoma
• Endometriosis
• Endometriosis-associated ovarian carcinoma
• Malignant endometriosis
• Pathology

• Adult
• C-Reactive Protein/analysis
• CA-125 Antigen/blood
• Endometriosis/blood
• Female
• Hemoglobins/analysis
• Humans
• Pelvis
• Retrospective Studies

• Carcinoma, Ovarian Epithelial/etiology
• Carcinoma, Ovarian Epithelial/therapy
• Endometriosis/complications
• Female
• Humans
• Inflammasomes/physiology
• Ovarian Neoplasms/etiology
• Ovarian Neoplasms/therapy

• Endometriosis
• Ferroptosis
• Inflammation
• Iron
• Reactive oxygen species

• Biomarkers
• Endometriosis-associated ovarian cancer
• KRAS
• SIRT1

• HNF1β
• NF-κB
• antiapoptotic gene
• apoptosis
• endometriosis
• oxidative stress

We describe an extremely rare case of a borderline tumor arising from an extragonadal giant endometrial cyst. A 41-year-old woman complaining of abdominal pain was referred to our hospital with a diagnosis of large ovarian tumor. Magnetic resonance imaging revealed a large cystic tumor approximately 27 cm × 9 cm in area. The cyst contents were largely removed by suction, and then the tumor was resected laparoscopically. Both adnexa were normal in size and location. The tumor did not originate from the ovaries, and it was adherent only to the bilateral uterosacral ligaments and uterine body. The postoperative histopathological evaluation confirmed the presence of endometrioid borderline tumor with transition from endometriosis. Staging laparotomy was performed, and no remnant tumor was detected. This case is extremely unusual because such a large cystic tumor originating from extragonadal endometriosis is very rare, as is endometrioid borderline tumor arising from endometriosis.

• Atypical endometriosis
• endometrioid borderline tumor
• endometriosis-related ovarian neoplasm
• extragonadal endometriosis