Prevalence of Lynch syndrome in women with mismatch repair-deficient ovarian cancer

Abstract

Background: There are limited data on the prevalence of Lynch syndrome (LS) in women with primary ovarian cancer with mismatch repair deficiency (MMR-D) by immunohistochemistry (IHC). Materials and Methods: Three hundred and eight cases of primary ovarian, fallopian, and peritoneal cancer between January 2012 and December 2019 were evaluated for MMR-D by IHC. The incidence of LS in this cohort was evaluated. Results: MMR-D by IHC was identified in 16 of 308 (5.2%) (95% CI: 3.2%–8.3%) primary ovarian-related cancers. Most cases with MMR-D were endometrioid (n = 11, 68.7%); (95% CI: 44.2%–86.1%). MSH2/MSH6 protein loss was detected in eight cases (50.0%); (95% CI: 28.0%–72.0%) and MLH1/PMS2 protein loss was detected in four cases (25.0%); (95% CI: 9.7%–50.0%). MSH6 protein loss was detected in two cases (12.5%); (95% CI: 2.2%–37.3%) and PMS2 protein loss was detected in two cases (12.5%); (95% CI: 2.2%–37.3%). All four cases with MLH1/PMS2 protein loss had MLH1 promotor hypermethylation. All 12 women with ovarian cancer suggestive of LS underwent germline testing and 8 (66.6%); (95% CI: 38.8%–86.5%) were confirmed to have LS. Conclusions: Most ovarian cancers with somatic MMR-D were confirmed to have LS in this cohort. Germline testing for LS in addition to BRCA1/2 for all women with an epithelial ovarian cancer would be efficient and would approach 100% sensitivity for identifying Lynch syndrome. Utilization of a multigene panel should also be considered, given the additional non-Lynch germline mutation identified in this cohort.