Objective: Lynch syndrome (LS) is characterized by a high lifetime incidence of colorectal cancer and gynecologic malignancies such as endometrial and ovarian cancer. Identification of LS families is important as it allows for heightened cancer screening which decreases colorectal cancer mortality. The original 1996 Bethesda guidelines included two gynecologic populations that should be further evaluated for LS: those with endometrial cancer before the age of 45 years and those with two LS-related cancers (i.e. synchronous endometrial and ovarian cancer). Our study aims to estimate the prevalence of LS in these two populations.
Methods: We utilized a diagnostic algorithm that included immunohistochemistry for mismatch repair protein expression followed by selective evaluation for microsatellite instability and MLH1 gene promoter methylation.
Results: Among 72 eligible patients, 9 (12%) had molecular findings consistent with LS: 6/50 (12%) in the early-onset endometrial cancer group and 3/22 (14%) in the synchronous primary cancer group. In an additional 3 cases, MLH1 silencing was due to promoter methylation: 1/50 (2%) in the early-onset endometrial cancer group and 2/22 (9%) in the synchronous primary cancer group. Of the 9 women with molecular criteria suggesting LS, only three had pedigrees meeting the Amsterdam criteria.
Conclusions: A diagnostic algorithm can identify patients with LS and those who warrant further genetic testing. Our findings reinforce the recommendation that women diagnosed with endometrial cancer before the age of 45 years and women with synchronous endometrial and ovarian cancer be screened for LS, irrespective of family history.