Cellular models of development of ovarian high‐grade serous carcinoma: A review of cell of origin and mechanisms of carcinogenesis

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

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Clinical Outcomes of Patients with High-Grade Ovarian Carcinoma Arising in Endometriosis Compared to Ovarian High-Grade Serous Carcinoma

Indian Journal of Gynecologic Oncology ◽

10.1007/s40944-021-00559-z ◽

2021 ◽

Vol 19 (4) ◽

Author(s):

Ibrahim Yalcin ◽

Hanifi Sahin ◽

Mustafa Erkan Sari ◽

Asuman Nihan Haberal ◽

Eda Adeviye Sahin ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Clinical Outcomes ◽

Serous Carcinoma ◽

High Grade

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Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom

Diagnostics ◽

10.3390/diagnostics11030547 ◽

2021 ◽

Vol 11 (3) ◽

pp. 547

Author(s):

Iolia Akaev ◽

Siavash Rahimi ◽

Olubukola Onifade ◽

Francis John Edward Gardner ◽

David Castells-Rufas ◽

...

Keyword(s):

Ovarian Cancer ◽

Unknown Origin ◽

Parp Inhibitors ◽

Serous Carcinoma ◽

High Grade ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Epithelial Cancers ◽

Pathogenic Variants ◽

Pathogenic Mutations

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

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Combined CCNE1 high‐level amplification and overexpression is associated with unfavourable outcome in tubo‐ovarian high‐grade serous carcinoma

The Journal of Pathology Clinical Research ◽

10.1002/cjp2.168 ◽

2020 ◽

Vol 6 (4) ◽

pp. 252-262

Author(s):

Angela MY Chan ◽

Emeka Enwere ◽

John B McIntyre ◽

Holly Wilson ◽

Chidera Nwaroh ◽

...

Keyword(s):

Serous Carcinoma ◽

High Grade ◽

Unfavourable Outcome ◽

High Level

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