The clinical features and management of Lynch syndrome‐associated ovarian cancer

Abstract

Aim Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, characterized by mutations in mismatch repair genes and autosomal dominant inheritance. Women with LS have an additional increased risk of gynecologic malignancies, including endometrial cancer (EC) and ovarian cancer (OC). Compared with EC, OC is relatively under investigation. This review thoroughly summarizes the current clinical evidence of surveillance, screening, and prevention strategies, and describes the molecular and clinical characteristics of LS‐associated OC. Methods An electronic search from databases of PubMed and Google Scholar was carried out using key words pertaining to Lynch syndrome and ovarian cancer. A review of the literatures including review articles, experimental, and observational studies published between 2000 and 2021 was conducted. Results The lifetime risk of OC in women with LS of MLH1, MSH2, and MSH6 mutations is approximately 7%, with the median age at onset being 46 years, 10–15 years earlier than that in sporadic cases. Histologically, LS‐associated OCs are primarily endometrioid (40%), high‐grade (25%), and low‐grade (11%) serous, or clear cell (6%) in nature. Eighty‐five percent of patients are diagnosed at an early stage, presenting with a good prognosis at 84% 5‐year survival. Optimal screening strategies for OC in LS are controversial; combined screening of patients' clinical and family history, immunohistochemical analysis, and microsatellite instability testing for mismatch repair deficiency have been proven efficient. Conclusion The clinical features were different between ovarian cancer in Lynch syndrome and sporadic cases. More research are needed for a greater understanding of the prevention and medical treatment of LS‐associated OC.

SPOCK1 Overexpression Suggests Poor Prognosis of Ovarian Cancer

“…Germline or acquired mutations of the BRCA1 and BRCA2 genes results in the impairment of their proteins that are involved in the homologue recombination of DNA [ 1 ]. Among other heritable cancers, Lynch syndrome can also facilitate the development of ovarian cancer through missense mutations in mismatch repair genes [ 2 ]. However, the majority of ovarian tumors arise without inherited genetic mutations.…”