Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 140
Frontiers in oncology · Nov 2023
endometrial clear cell carcinomaendometrioid carcinoma
This observational study compared clinical features of 28 endometrial clear cell carcinoma (ECCC) patients with 112 endometrioid carcinoma patients and applied TCGA classification to 19 ECCCs. ECCC patients were older and had higher rates of myometrial invasion and LVSI; among ECCCs, LVSI was associated with poorer prognosis. Of 19 ECCCs, the TCGA subtypes included POLEmut (10.5%), MMRd (15.8%), p53wt (57.9%), and p53abn (15.8%); 31.6% were HER-2 positive and 42.1% had TAF1 expression loss. The authors report that HER-2 positivity and TAF1 loss were associated with worse outcomes in ECCC.
Reported effects: median age 64.5, n=28 · myometrial invasion rate 42.8%, n=28 · +7 more
Key findings
- ECCC had older age of onset (median age, 64.5 years, range 31-81 years).
- ECCC showed higher rate of myometrial invasion (42.8% vs. 21.5% in endometrioid carcinoma).
- ECCC showed higher LVSI (33% vs. 16%).
- Among the ECCCs, LVSI was a poor prognostic factor.
- TCGA classification of 19 ECCCs: POLEmut 10.5% (2/19), MMRd 15.8% (3/19), p53wt 57.9% (11/19), p53abn 15.8% (3/19).
- Of 19 ECCCs, six (31.6%) showed HER-2 positive expression and eight (42.1%) had TAF1 expression loss.
- The authors report ECCCs with HER-2 and TAF1 expression had worse outcomes.
Limitations: Small ECCC sample (28 cases; only 19 underwent TCGA classification).; Observational design without randomized or controlled assignment.; Abstract does not report numerical survival statistics (HRs, median survival) or multivariable analyses, limiting assessment of effect sizes and confounding..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMixed resultsLimited evidenceTier 4 · clinical
Journal of Cancer · Feb 2021 · narrative review
ovarian clear cell carcinomaepithelial ovarian carcinomaovarian endometrioid carcinoma
This review summarizes current knowledge about ovarian clear cell carcinoma (OCCC), including its link to endometriosis, distinctive clinical features (younger age at diagnosis, platinum resistance, higher venous thromboembolism risk), and typical metastatic patterns. The authors discuss diagnostic limitations (only mild CA125 elevation) and outline ongoing therapeutic research into targeted and immune-based approaches (PARP, EZH2, ATR inhibitors exploiting ARID1A deficiency; MAPK/PI3K/HER2; VEGF/bFGF/PDGF; HNF1β; and PD-1/PD-L1 inhibitors). They identify advanced stage, suboptimal cytoreduction, platinum resistance, lymph node metastasis, and VTE as major prognostic predictors.
Studied with: ARID1A deficiency (synthetic lethality).
Key findings
- OCCC is a distinct pathological subtype of epithelial ovarian carcinoma with high prevalence in Asia and lacks a specific molecular subtype classification.
- Endometriosis is a recognized precancerous lesion associated with an increased risk of developing OCCC.
- Ovarian endometrioid carcinoma shares features with OCCC, including platinum resistance and younger age at diagnosis.
- Patients with OCCC have a higher risk of venous thromboembolism compared with other epithelial ovarian cancers.
- OCCC more commonly metastasizes via lymphatic, vesicular, and peritoneal spread rather than hematogenous spread.
- Conventional biomarker CA125 shows only mild elevation in OCCC, limiting its diagnostic utility.
- Standard management includes staging surgery or optimal cytoreduction combined with chemotherapy, but platinum resistance portends poor prognosis.
- Targeted therapies and immunotherapies under study include PARP, EZH2, ATR inhibitors (leveraging ARID1A deficiency), MAPK/PI3K/HER2-directed agents, VEGF/bFGF/PDGF inhibitors, HNF1β-targeted strategies, and PD-1/PD-L1 inhibitors.
- Advanced stage, suboptimal cytoreduction, platinum resistance, lymph node metastasis, and VTE are major prognostic predictors for OCCC.
Limitations: This work is a review (no original experimental or patient-level data are presented).; Many therapeutic strategies discussed are 'currently being studied' — evidence for efficacy in OCCC is early or not yet established.; OCCC lacks a specific molecular subtype classification, limiting precision therapeutic targeting.; Diagnostic reliance on CA125 is limited because CA125 is only mildly elevated in OCCC..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
ReviewMechanismInconclusiveModerate evidenceTier 4 · clinical
Surgical pathology clinics · Jun 2019 · narrative review
ovarian endometrioid carcinomaovarian clear cell carcinomahigh-grade serous carcinoma
This narrative review summarizes current knowledge about ovarian endometrioid and clear cell carcinomas. It highlights their associations with endometriosis and Lynch (HNPCC) syndrome and notes that both typically present at an early stage. The review discusses pathologic and immunohistochemical features that help distinguish these tumors from high-grade serous carcinomas and from each other, and covers staging, grading, and aspects of molecular pathogenesis.
Key findings
- Endometrioid and clear cell carcinomas of the ovary are associated with endometriosis.
- Both histotypes show an association with hereditary nonpolyposis colorectal cancer (Lynch) syndrome.
- These tumors typically present at an early stage.
- The review describes pathologic and immunohistochemical features that distinguish these tumors from high-grade serous carcinoma and from other mimics, and discusses staging, grading, and molecular pathogenesis.
Limitations: Review article — no new primary data presented; Abstract does not state whether this is a systematic review or the methodology used for literature selection; No quantitative synthesis or original outcome data reported in the abstract; Specific molecular mechanisms are not detailed in the abstract.
A pathology-focused review that summarizes diagnostic, staging/grading, and molecular-pathogenesis knowledge for ovarian endometrioid and clear cell carcinomas.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
ReviewMechanismInconclusiveLimited evidenceTier 3 · early human
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · Jan 2019 · literature review and consensus discussion at the 2016 Endometrial Cancer Workshop (International Society of Gynecological Pathologists)
high-grade endometrial carcinomaendometrioid carcinomaserous carcinomaclear cell carcinomaundifferentiated carcinomadedifferentiated carcinomacarcinosarcomaendometrial neoplasms
This article is a literature review plus consensus recommendations from an expert workshop on diagnostic issues in high-grade endometrial carcinomas. It summarizes morphologic criteria and recommended immunohistochemical markers to distinguish FIGO grade 3 endometrioid, serous, clear cell, undifferentiated/dedifferentiated carcinomas, and carcinosarcomas. The authors note that evidence supporting recommendations is weak-to-moderate because of small study sizes and nonuniform diagnostic criteria. Specific markers discussed include p53, p16, mismatch repair proteins, PTEN, ARID1A, Napsin A, p504s, PAX8, e-cadherin, and SWI-SNF proteins.
Key findings
- The review and workshop generated recommendations on diagnostic criteria for high-grade endometrial carcinomas, but levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria in many studies.
- FIGO grade 3 endometrioid carcinoma is defined as >50% solid architecture (excluding squamous areas), or an architecturally FIGO grade 2 tumor with marked cytologic atypia after exclusion of a glandular variant of serous carcinoma.
- The most useful immunohistochemical studies to distinguish FIGO grade 3 endometrioid versus serous carcinoma are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A.
- Endometrial clear cell carcinoma requires prototypical architectural and cytologic features for diagnosis; Napsin A and p504s are useful ancillary stains and aberrant p53 expression occurs in a minority of clear cell carcinomas.
- Clear cells can be present in all types of high-grade endometrial carcinomas, which can lead to overdiagnosis of clear cell carcinoma.
- Undifferentiated carcinoma (and dedifferentiated carcinoma when associated with low-grade endometrioid carcinoma) is composed of sheets of monotonous, typically dyscohesive cells, may have a rhabdoid appearance, often shows limited cytokeratin and EMA expression, is usually negative for PAX8 and hormone receptors, lacks membranous e-cadherin, and commonly demonstrates loss of DNA mismatch repair proteins and SWI-SNF proteins.
- Carcinosarcomas require unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation.
Limitations: This is a review and consensus from a workshop rather than a primary data study.; Authors state levels of evidence are weak or moderate due to small sample sizes in many underlying studies.; Nonuniform diagnostic criteria in the literature limit the strength of recommendations..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text