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Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

A study led by Cancer Research UK Edinburgh Centre researchers provides improved molecular taxonomy of endometrioid ovarian carcinoma and identifies candidate targets for molecular therapeutics: October 2020

Image showing classification of endometrioid ovarian carcinoma proposed by Hollis et al.

Ovarian carcinomas are a heterogeneous group of ovarian cancers comprising five core histological types, each with distinct pathological characteristics, molecular landscapes and clinical behaviour. Endometrioid ovarian carcinomas (EnOC) account for approximately 10% of all ovarian carcinomas. They are usually characterised as complex nonspecific solid-cystic masses and may be associated with endometriosis.

Currently, the management of EnOC follows the historic one-size-fits-all approach of aggressive cytoreductive surgery with adjuvant platinum–taxane chemotherapy for patients with disease that has progressed beyond the ovary/fallopian tube. By contrast, routine molecular stratification of care is emerging in other ovarian cancer types, most notably with the advent of poly-ADP ribose polymerase (PARP) inhibitor therapy.

In a recent study titled “Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome” investigators from the University of Edinburgh, Western General Hospital in Edinburgh and the Jikei University School of Medicine in Tokyo re-visited the classification of EnOC using an improved histopathology approach (to avoid confusing high grade EnOC with another ovarian cancer type - high-grade serous ovarian carcinoma) and whole exome sequencing (to obtain the detailed genomic landscape of the tumours analysed). This resulted in identification of subtypes of EnOC that display distinct clinical behaviour and construction of a step-wise taxonomy for EnOC classification based on mutation status of TP53 (a gene encoding the protein known as p53 which acts as a tumour suppressor) and CTNNB1 (a gene encoding the protein beta catenin which has been implicated in regulation of cell–cell adhesion and gene transcription). Cases with TP53 mutation demonstrated greater genomic complexity, were commonly FIGO (International Federation of Gynecology and Obstetrics) stage III/IV at diagnosis (48%), were frequently incompletely debulked (44%) and demonstrated inferior survival. Conversely, cases with CTNNB1 mutation, which was mutually exclusive with TP53 mutation, demonstrated low genomic complexity, excellent clinical outcome, and were predominantly stage I/II at diagnosis (89%) and completely resected (87%). The remaining cases represent a subtype with intermediate prognosis. The study also indicated that the WNT, MAPK/RAS and PI3K cellular signalling pathways may represent good candidate targets for molecular therapeutics in EnOC.

The work was published in the journal Nature Communications. It was led by investigators from the Nicola Murray Centre for Ovarian Cancer Research within the Cancer Research UK Edinburgh Centre and the MRC Institute of Genetics & Molecular Medicine.

Our work has the potential to inform future prognostication and molecular stratification of endometrioid ovarian carcinomas. It may also guide discovery of better therapeutics for these cancers

C. Simon HerringtonProfessor of Molecular Cancer Pathology and the corresponding author for the published study

Related Links:

Article in Nature Communications:

https://www.nature.com/articles/s41467-020-18819-5

Professor Simon Herrington group website:

https://www.ed.ac.uk/cancer-centre/research/herrington-group

Professor Charlie Gourley group website:

https://www.ed.ac.uk/cancer-centre/research/gourley-group

Information about ovarian cancer:

 https://www.cancerresearchuk.org/about-cancer/ovarian-cancer

Interesting presentation on genomic stratification of ovarian cancer:

https://www.youtube.com/watch?v=lLyQ01rtu_w

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