Genomic mutation features identify distinct BRCA-associated mutation characteristics in endometrioid carcinoma and endometrioid ovarian carcinoma

Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

npj Precision Oncology ◽

10.1038/s41698-021-00187-y ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Robert L. Hollis ◽

Barbara Stanley ◽

John P. Thomson ◽

Michael Churchman ◽

Ian Croy ◽

...

Keyword(s):

High Risk ◽

Ovarian Carcinoma ◽

Expression Patterns ◽

Parp Inhibitors ◽

Receptor Expression ◽

Cancer Type ◽

Sequencing Data ◽

Molecular Features ◽

Endometrioid Ovarian Carcinoma ◽

Molecular Landscape

AbstractEndometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy.

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Clinicopathological characterization of a real-world multicenter cohort of endometrioid ovarian carcinoma: Analysis of the French national ESME-Unicancer database

Gynecologic Oncology ◽

10.1016/j.ygyno.2021.07.019 ◽

2021 ◽

Author(s):

Alexandre De Nonneville ◽

Christophe Zemmour ◽

Sophie Frank ◽

Florence Joly ◽

Isabelle Ray-Coquard ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Real World ◽

Multicenter Cohort ◽

Endometrioid Ovarian Carcinoma

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Application of precision medicine: can molecular risk stratification provide new management options for low stage endometrioid ovarian carcinoma?

10.1136/ijgc-2019-esgo.41 ◽

2019 ◽

Author(s):

P Krämer ◽

A Talhouk ◽

T Bosse ◽

F Heitz ◽

S Prader ◽

...

Keyword(s):

Risk Stratification ◽

Ovarian Carcinoma ◽

Precision Medicine ◽

Management Options ◽

Endometrioid Ovarian Carcinoma

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Molecular Heterogeneity of Endometrioid Ovarian Carcinoma

The American Journal of Surgical Pathology ◽

10.1097/pas.0000000000001478 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Cited By ~ 1

Author(s):

Susanna Leskela ◽

Ignacio Romero ◽

Juan M. Rosa-Rosa ◽

Tamara Caniego-Casas ◽

Eva Cristobal ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Molecular Heterogeneity ◽

Endometrioid Ovarian Carcinoma

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Ethnic variations in ARID1a expression in clear cell and endometrioid ovarian carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e17073 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e17073-e17073

Author(s):

Tiffany Lai ◽

Koah Vierkoetter ◽

Asia Ayabe ◽

Hyeong Jun Ahn ◽

David Shimizu ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Clear Cell ◽

Endometrioid Ovarian Carcinoma ◽

Ethnic Variations

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The effect of lymphadenectomy and adjuvant chemotherapy on survival in stage I, grade 1 and 2 endometrioid ovarian carcinoma

Gynecologic Oncology ◽

10.1016/s0090-8258(21)01205-1 ◽

2021 ◽

Vol 162 ◽

pp. S291

Author(s):

Brenna Swift ◽

Allan Covens ◽

Victoria Mintspoulos ◽

Carlos Parra-Herran ◽

Marcus Bernardini ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Ovarian Carcinoma ◽

Stage I ◽

Endometrioid Ovarian Carcinoma

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Clear cell/endometrioid type ovarian carcinoma associated with endometriosis of the ipsilateral ovary

Vojnosanitetski pregled ◽

10.2298/vsp170424107r ◽

2019 ◽

Vol 76 (5) ◽

pp. 547-551

Author(s):

Ivana Rudic-Biljic-Erski ◽

Mladenko Vasiljevic ◽

Snezana Rakic ◽

Olivera Dzatic-Smiljkovic ◽

Sladjana Mihajlovic

Keyword(s):

Ovarian Carcinoma ◽

Clear Cell ◽

Early Stage ◽

Psoas Muscle ◽

Disease Recurrence ◽

Good Prognosis ◽

Ovarian Endometriosis ◽

Muscle Region ◽

Endometrioid Ovarian Carcinoma ◽

The Right

Introduction. Ovarian endometriosis has been identified as a risk factor for occurrence of endometriosis-associated ovarian carcinoma. We presented a rare case of simultaneous clear cell/ endometrioid ovarian carcinoma and endometriosis of the ipsilateral ovary. Case report. A 47-yearold patient underwent surgery for right ovarian endometriotic cyst. A total hysterectomy with bilateral salpingooophorectomy, lymphadenectomy in the right psoas muscle region and omentectomy were performed as well as multiple peritoneal biopsies. Six cycles of chemotherapy were instituted postoperatively using the Taxol-CBDCA protocol. Abdominal and pelvic CT did not demonstrate recurrence of the disease postoperatively and after completed chemotherapy treatment. Six months after the completion of treatment, the patient felt well without the disease recurrence. Conclusion. Clear cell and endometrioid subtypes of ovarian carcinoma have good prognosis if they are diagnosed and treated at an early stage of the disease. In our patient, the carcinoma was detected in the first stage and successfully treated with combination therapy, i.e., surgical and chemotherapy.

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Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

Nature Communications ◽

10.1038/s41467-020-18819-5 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Robert L. Hollis ◽

John P. Thomson ◽

Barbara Stanley ◽

Michael Churchman ◽

Alison M. Meynert ◽

...

Keyword(s):

Clinical Outcome ◽

Ovarian Carcinoma ◽

Molecular Taxonomy ◽

Figo Stage ◽

Molecular Heterogeneity ◽

Molecular Stratification ◽

Genomic Complexity ◽

Molecular Therapeutics ◽

Whole Exome ◽

Endometrioid Ovarian Carcinoma

Abstract Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency of mutation in CTNNB1 (43%), PIK3CA (43%), ARID1A (36%), PTEN (29%), KRAS (26%), TP53 (26%) and SOX8 (19%), a recurrently-mutated gene previously unreported in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy is constructed, identifying clinically distinct EnOC subtypes: cases with TP53 mutation demonstrate greater genomic complexity, are commonly FIGO stage III/IV at diagnosis (48%), are frequently incompletely debulked (44%) and demonstrate inferior survival; conversely, cases with CTNNB1 mutation, which is mutually exclusive with TP53 mutation, demonstrate low genomic complexity and excellent clinical outcome, and are predominantly stage I/II at diagnosis (89%) and completely resected (87%). Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.

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