Abstract
Besides BRCA1 and BRCA2, several other inheritable mutations have been identified that increase ovarian cancer risk. Surgical excision of the fallopian tubes and ovaries reduces ovarian cancer risk, but for some non-BRCA hereditary ovarian cancer mutations the benefit of this intervention is unclear. The fallopian tubes of women with hereditary ovarian cancer mutations provide many insights into the early events of carcinogenesis and process of malignant transformation. Here we review cancer pathogenesis in hereditary cases of ovarian cancer, the occurrence of pre-invasive lesions and occult carcinoma in mutation carriers and their clinical management.
Highlights
Familial or hereditary ovarian cancer syndromes (HOC) encompass a number of tumor suppressor genes in which heritable mutations together account for 24% of epithelial ovarian cancer cases [1]
BRCA1-mutated luteal phase fallopian tubes demonstrate differential expression of more than 100 inflammation-related and NF-κB signaling genes compared to post-ovulatory non-mutation carriers which likely contributes to tumorigenesis [45]
Ovarian cancer pathogenesis in hereditary cases begins with altered responses to inflammation and cellular stress in the fallopian tube which occur in the context of cyclic hormonal control and ovulation
Summary
Familial or hereditary ovarian cancer syndromes (HOC) encompass a number of tumor suppressor genes in which heritable mutations together account for 24% of epithelial ovarian cancer cases [1]. In 2001, Piek et al first reported dysplastic changes in the fallopian tube epithelia (FTE) of BRCA mutation carriers undergoing risk-reducing surgery [28]. These lesions, termed serous tubal intraepithelial carcinoma (STIC), the immediate precursor to HGSC arise from secretory cells, have p53 mutation with strong immunohistochemical staining and are highly proliferative [2,23,25,29,30,31]. We discuss pre-neoplastic lesions and occult carcinoma occurring in women with BRCA mutations as well as other rare and recently described HOC mutations and describe the early events in carcinogenesis in this population
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