Endometrial cancer and Lynch syndrome: clinical and pathologic considerations

Abstract

Background: Approximately 2% to 5% of endometrial cancers may be due to an inherited susceptibility. Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, an autosomal-dominant inherited cancer susceptibility syndrome caused by a germline mutation in one of the DNA mismatch repair genes, accounts for the majority of inherited cases. Lynch syndrome is associated with early onset of cancer and the development of multiple cancer types, particularly colon and endometrial cancer.

Methods: The current status of knowledge regarding Lynch syndrome-associated endometrial cancer and methods for diagnosis, screening, and prevention of cancers is reviewed.

Results: The lifetime cumulative risk of endometrial cancer for women with Lynch syndrome is 40% to 60%, which equals or exceeds their risk of colorectal cancer. No current evidence suggests either a survival advantage or disadvantage to endometrial cancer that is associated with Lynch syndrome when these cases are compared with sporadic cases. A combination of family and personal medical history and tumor testing provides an efficient basis for diagnosing Lynch syndrome in women with endometrial cancer. Current gynecologic cancer screening guidelines for women with Lynch syndrome include annual endometrial sampling and transvaginal ultrasonography beginning at age 30 to 35 years.

Conclusions: Diagnosing endometrial cancer patients with Lynch syndrome has important clinical implications for the individual and family members. Screening and prevention practices can decrease the likelihood of developing additional cancers.

Fig 1A-C

(A) Endometrioid endometrial carcinoma hematoxylin-eosin stain from a patient with Lynch Syndrome/hereditary nonpolyposis colorectal cancer (10 × power). (B) Endometrioid endometrial carcinoma from a patient with Lynch syndrome/HNPCC staining positively for hMLH1. (C) Endometrioid endometrial carcinoma from a patient with Lynch syndrome/HNPCC staining negatively for hMSH2. Courtesy of Russell R. Broaddus, MD, PhD.

Fig 2

Representative MSI chromatogram for the microsatellites BAT25, BAT26, and BAT40. The tumor DNA (lower tracing for each microsatellite) demonstrates an increased number of peaks compared with the DNA extracted from nonneoplastic tissue from the same patient (upper tracing for each microsatellite). Therefore, allelic shift is present for these 3 microsatellites. If a tumor exhibits such allelic shift in 2 or more of the panel of 7 microsatellites, the tumor is considered MSI-high. Courtesy of Russell R. Broaddus, MD, PhD.