Pathological Features of Endometrial Cancer in Patients with Lynch Syndrome
J Palacios, C Alenda, D Lujan, C Cordero, E Mendoza, P Trillo, JL Soto. Hospital Universitario Virgen del Rocio, Seville, Spain; Hospital Universitario de Alicante, Alicante, Spain; Hospital General Universitario de Elche, Elche, Spain
Background: The incidence of endometrial cancer (EC) in women with Lynch syndrome (LS) equals or exceeds that of colorectal cancer (CRC) and in more than 50% of cases these women present with a gynaecological cancer as the first or sentinel malignancy. Although pathological characteristics of CRC in LS patients are well documented, there are few studies analyzing pathological features in LS patients with documented germline mutations.
Design: The pathological features of 16 ECs found in patients with LS (mean age 44.9 years) with documented germline mutation in MLH1 (8 patients), MSH2 (6 patients) or MSH6 (2 patients) genes were compared with those observed in a series of 28 EC found in patients 50 years old or younger (mean age 46.2 years). Histological type and grade, deep of myometrial invasion, presence of vascular invasion, peritumoral lymphocytes, tumor infiltrating lymphocytes (TILs), and the presence of Cronh-like aggregates were compared between both groups.
Results: Amomg LS-ECs, 6 (37%) had a non-endometrioid (serous or clear cell) component, 7 (46%) extensive peritumoral lymphocyte infiltration and 8 (50%) more than 40 TILs/10 HPFs, but these characteristic were only found in 4 (14%), 3 (10.7%) and 5 (17.8%) control ECs (p<0.05 for all comparisons). There were no statistical significant differences in the frequency of all other variables analyzed, although LS-ECs were more frequently grade 3 (20% vs 8%) and showed more frequently Cronh-like aggregates (27% vs 18%). Immnohistochemistry analysis of MLH1, PMS2, MSH2 and MSH6 was concordant with the genetic alteration in LS-ECs. In addition, we found 5 MSH1/PMS2-negative and 2 MSH2/MSH6-negative cases (presumptive LS patients) among control ECs.
Conclusions: Tumour pathological features together with age and familial history of LS-associated cancers can help in selecting tumors for the study of expression of MLH1, PMS2, MSH2 and MSH6 by immunohistochemistry and to select women with EC for LS genetic testing.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 1:45 PM
Platform Session: Section C, Monday Afternoon