Germline mutation in either BRCA1 or BRCA2 is associated with an increased risk of ovarian cancer, particularly the most common invasive histotype - serous carcinoma.
Recently, studies of women with BRCA1 or BRCA2 mutations (BRCA+) undergoing risk reducing salpingo-oophorectomy have highlighted the distal fallopian tube as a common (80%) site of tumor origin and additional studies of unselected women with pelvic serous carcinoma have demonstrated that serous tubal intraepithelial carcinoma may precede a significant percentage of these tumors.
Current data indicate that each of these histologic subtypes is associated with distinct morphologic and molecular genetic alterations: high-grade serous and possibly endometrioid carcinomas most probably arise from surface epithelial inclusion glands with TP53 mutations and dysfunction of BRCA1 and/or BRCA2; low-grade serous carcinomas probably arise in a stepwise fashion in an adenoma-borderline tumor-carcinoma sequence from typical to micropapillary borderline tumors to low-grade invasive serous carcinoma via activation of the RAS-RAF signaling pathway secondary to mutations in KRAS and BRAF; mucinous carcinomas arise via an adenoma-borderline tumor-carcinoma sequence with mutations in KRAS; low-grade endometrioid carcinomas arise from endometriosis via mutations in CTNNB1 (the gene encoding beta-catenin) and PTEN.