Clinicopathologic Features of Sporadic Endometrial Carcinomas with MLH1 Promoter Hypermethylation: A Study of 54 Cases.
Anne M Mills, Reetesh K Pai, Sophia Liou, Teri A Longacre. Stanford University, CA
Background: MLH1 protein deficiency due to epigenetic silencing of MLH1 by promoter hypermethylation occurs frequently in endometrial carcinomas, but the clinicopathologic features of these tumors have not been well characterized.
Design: Fifty-four endometrial carcinomas with deficient MLH1 immunohistochemical expression resulting from MLH1 promoter methylation identified by real-time PCR (Methylight) DNA methylation analysis were studied. Tumors were assessed for histologic type, grade, lymphovascular invasion, tumor infiltrating lymphocytes, depth of invasion, concurrent hyperplasia, tumor location, and stage.
Results: The average patient age was 64.8 years (range: 42-88). The majority (86%, 44/51) of tumors were located in the uterine fundus. Four tumors were located in the fundus with extension into the lower uterine segment (LUS) while 3 tumors were limited to the LUS. While most tumors (81%, 44/54) showed pure endometrioid histology, 19% (10/54) also demonstrated mucinous differentiation. No serous, clear cell, or carcinosarcoma histologies were identified. Most tumors were either grade 1 (41%, 22/54) or grade 2 (42%, 23/54); only 9 cases were high grade. One endometrioid case showed predominantly grade 1 tumor immediately juxtaposed with a focus of undifferentiated carcinoma. Advanced FIGO stage was seen in 13% of grade 1, 24% of grade 2, and 44% of grade 3 carcinomas. Tumor-infiltrating lymphocytes were present in 33%. At least 35% had concurrent hyperplasia and in no instance was the hyperplastic component associated with loss of MLH1.
Conclusions: Sporadic endometrial carcinoma with MLH1 promoter hypermethylation occurs predominantly in the uterine fundus, is associated with endometrioid or mucinous histology – often with associated hyperplasia, and exhibits a similar grade distribution to non-MLH1 methylated endometrial cancer. Despite decreased high-risk histology, MLH1-methylation appears to be associated with an increased rate of advanced-stage disease.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 156, Wednesday Afternoon