Lynch Syndrome Screening in a Series of 869 Prospective Colorectal Carcinomas
E Musulen, C Sanz, A Munoz-Marmol, L Benito, JL Mate, A Ariza. Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Institut Catala d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain
Background: According to the Bethesda guidelines, presentation of colorectal carcinoma (CRC) before age 50 and presentation of mucinous or medullary (M/M) CRC before age 60 are both criteria to suspect Lynch syndrome (LS). The aim of the present study was to evaluate the efficiency of these two criteria.
Design: A series of 869 prospectively resected primary CRCs was studied. In all cases the following scheme was applied: (i) immunohistochemistry for mismatch repair protein genes (MLH1, MSH2, and MSH6); (ii) microsatellite instability (MSI) analysis amplifying five different microsatellites (NR21, NR24, NR27, bat25, and bat26) when all three MLH1, MSH2, and MSH6 were positive in CRC patients younger than 50 and in M/M CRC patients younger than 60; and (iii) sequencing study of the V600E B-raf gene mutation in MLH1(-) cases. CRC was considered to be probably LS-related when showing one of the following profiles: (i) MSH2 (-) and MSH6 (-); (ii) MSH6 (-); (iii) MLH1 (-) with wild type B-raf gene; or (iv) MSI-H (≥ than 2 mutated microsatellites).
Results: Of the patients studied, 81 were under 50 years of age, 77 showed M/M CRC, 93 met suspicious criteria, and 45 showed probably LS-related CRC. Young age (<50 years) and M/M CRC proved to be strong risk factors with statistical significance (p=0.029 and p=0.000). Of the 45 patients with probably LS-related CRC, only 10 met Bethesda criteria.
Conclusions: Screening for LS should not be limited to patients meeting the Bethesda criteria, but should be performed in every case of CRC.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 85, Tuesday Afternoon