Abstract
High-grade serous carcinoma (HGSC) is the most common and aggressive histotype of epithelial ovarian cancer (EOC), and it is the predominant histotype associated with hereditary breast and ovarian cancer syndrome (HBOC). Mutations in BRCA1 and BRCA2 are responsible for most of the known causes of HBOC, while mutations in mismatch repair genes and several genes of moderate penetrance are responsible for the remaining known hereditary risk. Women with a history of familial ovarian cancer or with known germline mutations in highly penetrant genes are offered the option of risk-reducing surgery that involves the removal of the ovaries and fallopian tubes (salpingo-oophorectomy). Growing evidence now supports the fallopian tube epithelia as an etiological site for the development of HGSC and consequently, salpingectomy alone is emerging as a prophylactic option. This review discusses the site of origin of EOC, the rationale for risk-reducing salpingectomy in the high-risk population, and opportunities for salpingectomy in the low-risk population.
Highlights
In 2015, approximately 22,000 women in the United States were diagnosed with ovarian cancer and 14,000 died from this devastating disease [1]
Of the patients diagnosed with a high-grade serous carcinoma (HGSC), 15–20% will have a known germline mutation in the highly penetrant homologous repair pathway genes, BRCA1 or BRCA2
A series of transcriptional studies by Tone et al and George et al have shown that the phenotypically normal fallopian tube epithelia from BRCA1 and BRCA2 mutation carriers show transcriptional differences when compared to epithelial cells with a normal BRCA genotype
Summary
High-grade serous carcinoma (HGSC) is the most common and aggressive histotype of epithelial ovarian cancer (EOC), and it is the predominant histotype associated with hereditary breast and ovarian cancer syndrome (HBOC). Mutations in BRCA1 and BRCA2 are responsible for most of the known causes of HBOC, while mutations in mismatch repair genes and several genes of moderate penetrance are responsible for the remaining known hereditary risk. Women with a history of familial ovarian cancer or with known germline mutations in highly penetrant genes are offered the option of risk-reducing surgery that involves the removal of the ovaries and fallopian tubes (salpingo-oophorectomy). Growing evidence supports the fallopian tube epithelia as an etiological site for the development of HGSC and salpingectomy alone is emerging as a prophylactic option.
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