Detection of Lynch Syndrome in Endometrial Cancer Patients

Abstract

Lynch syndrome (LS) is an autosomal dominant inherited disease defined by germline mutations in mismatch repair (MMR) genes, leading to a defective DNA MMR system. Patients with LS have predisposition to a spectrum of cancers, primarily colorectal cancer, but LS-associated endometrial cancer (LS-EC) is the most common extraintestinal cancer and occurs in 2% of LS patients. The most frequently mutated MMR genes are MLH1, MSH2, MSH6 and PMS2. Clinico-pathologic features of LS-EC are: early age of onset, lower body mass index, endometrioid type of carcinoma and lower uterine segment involvement.Recent studies support LS screening in every EC patient since MMR status is also part of the molecular subclassification of endometrial cancers. Screening methods include traditional clinical criteria and molecular techniques, such as MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1promoter methylation testing and gene sequencing. MSI can also be detected in sporadic tumors, through epigenetic events inactivating the MMR system.Patients with diagnosed LS and their affected relatives should be closely monitored in order to prevent the development of other types of cancer. Patients with advanced recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) endometrial cancer can also benefit from immunotherapy.We describe our 3-year experience in screening of Lynch syndrome in EC patients.