Ovarian cancers generally develop from one of 3 cell types: epithelial cells, sex-cord stromal cells, or germ cells.
- Stromal and germ cell tumors are relatively uncommon, comprising fewer than 10% of cases.4
- The most common of these, that rising from epithelial cells, is also the most lethal form.7
The etiology of ovarian cancer is unknown. Genetic, morphologic and molecular data divide ovarian cancers into 2 groups.8
- Type I — low-grade serous carcinoma, endometrioid, mucinous and clear cell carcinomas
- Characterized by slow growth and multiple oncogenetic mutations (ie, KRAS, BRAF, PTEN and ARID1A)
- Type II — high-grade serous and endometrioid carcinomas, carcinosarcomas and undifferentiated carcinomas
- Characterized by aggressive growth, TP53 mutations, and a high level of chromosomal disruption
- While approximately 13% of HGSCs result from germline mutations in BRCA1/2, an integrated genomic analysis demonstrated that TP53 was mutated in at least 96% of HGSC samples.6
- Cancer-related signaling pathways that were dysregulated included the RB1 (67%), PI3K/RAS (45%) and homologous recombination (HR) pathways (~50%).6
The risk of developing ovarian cancer may be increased in women with BRCA1/2 mutations.
- Ovarian cancer penetrance is 41% to 46% for BRCA1 and 17% to 23% for BRCA2 mutations.9