Lynch Syndrome Screening Should Be Considered for All Patients with Newly Diagnosed Endometrial Cancer.
Anne M Mills, Sofia Liou, James M Ford, Jonathan S Berek, Reetesh K Pai, Teri A Longacre. Stanford University, CA
Background: Lynch syndrome (LS) is characterized by a high lifetime incidence of colorectal cancer and endometrial cancer. Given recent recommendations for universal, cost effective screening of all patients with newly diagnosed colorectal cancer using mismatch (MMR) protein immunohistochemistry (IHC), we evaluated for LS endometrial cancer in the general population.
Design: 387 consecutive cases of primary endometrial cancer at a single institution (1997-2010) were evaluated for LS regardless of age, family history or histologic features. Evaluation methods consisted of IHC for the MMR proteins MLH1, MSH2, MSH6 and PMS2, followed by real-time PCR (Methylight) DNA methylation analysis for cases with MLH1/PMS2 deficiency. A subset of tumors also had microsatellite instability and/or gene sequencing data, but this was not part of the study design.
Results: Twenty-six LS-associated endometrial cancers were identified: 2 MLH1/PMS2, and 24 with MSH6 and/or MSH2. Only 26% occurred in women <50 years of age (range, 39-88 years), one of which was in a prophylactic hysterectomy specimen for prior diagnosis of LS. Two had associated colorectal carcinoma, but there were no simultaneous ovarian carcinomas. 48% were grade 1; 26% grade 2; and 26% high grade. Most were endometrioid (n=21), with 2 mixed endometrioid/mucinous, 1 mucinous, 1 serous, 1 clear cell, and 1 carcinosarcoma. 3 were in the lower uterine segment; 9 had tumor infiltrating lymphocytes.
Conclusions: Screening using current Bethesda guidelines and recently suggested pathologic guidelines misses a substantial proportion of patients with MMR protein deficient endometrial cancer and many patients with LS. Based on recent recommendations for universal screening of newly diagnosed colorectal carcinomas, these data also support universal screening of all newly diagnosed endometrial cancer. A cost effective algorithm using only 2 MMR antibodies as an initial screen is proposed.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 161, Wednesday Afternoon