Rachel Hodan1,2, Kerry Kingham1,2, Kristina Cotter2, Ann K Folkins3, Allison W Kurian1,4,5, James M Ford1,4,6, Teri Longacre3. 1. Cancer Genetics and Genomics, Stanford Health Care, Stanford, CA, USA. 2. Department of Pediatrics (Genetics), Stanford University School of Medicine, Stanford, CA, USA. 3. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. 4. Department of Oncology, Stanford University School of Medicine, Stanford, CA, USA. 5. Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA. 6. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
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.
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.
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