Identifying Lynch Syndrome in Women Presenting With Endometrial Carcinoma Under the Age of 50 Years

Background: Lynch syndrome (LS) is an inherited disorder associated with genetic predisposition to endometrial, colorectal, ovarian, and other cancers. There is consensus for the necessity of assessment forLS inviewof the established survival benefits for identified patients and affected family members. The debate regarding the best screening policy is far from being concluded. Objectives: The aim of this study was to evaluate a realistic protocol for identifying LS families by assessing young women with a diagnosis of endometrial cancer (EC). Methods: Consecutive cases of women with a diagnosis of endometrioid EC younger than 50 years were recruited. A complete 3-generation pedigree was drawn and assessed against the Amsterdam II criteria. Tumor DNA microsatellite instability and immunohistochemistry testing for the expression of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2 was offered to all patients. MLH1 gene promoter methylation and EPCAM gene deletion testing were also offered where appropriate. Genetic counseling and MMR germline mutation tests were offered in women with abnormal results. Results: Fifty-eight women were invited, and 38 (65.5%), consented for LS assessment (95% confidence interval CI 53%-78%). A complete data set was obtained in 35 women (60.3%). Lynch syndrome according to clinical and/or molecular characteristics was diagnosed in 8 cases or 22.8% (95% CI 15%-48%). There was no significant difference at the age of women with a diagnosis of LS (median, 45 years; range, 37-48 years) compared with that of the non-LS ones (median, 45 years; range, 31-49 years). Three pathogenic MMR mutations were identified in the 8 cases with a diagnosis of LS, 37.5% (95% CI 5%-72%), estimating an 8.5% (95% CI 1%-19%) mutation prevalence in the study population. Conclusions: All women with newly diagnosed EC should be assessed for inherited predisposition. Regional policies for assessment should be developed in accordance with available resources. Gynecologists are required to upgrade their skills in order to identify, assess, and counsel patients with suspected or established LS and appropriately refer to clinical genetics.