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Review
. 2022 Feb 4;11(3):539.
doi: 10.3390/cells11030539.

Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2

David Samuel  1   2 , Alexandra Diaz-Barbe  3 , Andre Pinto  2   4 , Matthew Schlumbrecht  1   2 , Sophia George  1   2
Affiliations
Review

Hereditary Ovarian Carcinoma: Cancer Pathogenesis Looking beyond BRCA1 and BRCA2

David Samuel et al. Cells. .

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.

Keywords: ATM; BRCA1; BRCA2; BRIP1; MRE11; NBN; PALB2; RAD50; RAD51; STIC; carcinogenesis; hereditary breast and ovarian cancer syndrome; ovarian cancer pathogenesis; serous tubal intraepithelial carcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
DNA repair pathways with genes associated with hereditary ovary cancer and their risk assessment according to the 2019 NCCN guidelines. Created with Biorender.
Figure 2
Figure 2
Histologic features of HGSC precursor lesions occurring in the fallopian tube. (A) p53 signature: hematoxylin and eosin (H&E) staining shows a single layer of cells, mostly non-ciliated, with abundant cytoplasm and bland cytologic features. (B) Serous tubal intraepithelial lesion (STIL): H&E shows non-stratified lining and lack of conspicuous nuclear atypia and is non-diagnostic for intraepithelial carcinoma. (C) Serous Tubal Intraepithelial Carcinoma (STIC): H&E shows the distal fallopian tube epithelium demonstrates absent cilia, loss of polarity and marked cytologic atypia. (D–F) Immunohistochemistry for p53 of the above sections shows aberrant staining and overexpression, a feature common to all tubal HGSC precursor lesions.
See this image and copyright information in PMC

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