Defective mismatch-repair as a minor turnorigenic pathway in Barrett esophagus-associated adenocarcinorna

The malignant transformation that characterizes the development of Barrett esophagus-associated adenocarcinomas is a multi-step process in which genetic alterations in various tumor-associated genes accumulate. Defective mismatch repair (MMR) is the cause of microsatellite instability (NISI) pathway that characterizes a subset of gastrointestinal tumors and is specifically associated with tumor development within the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. The few studies that have assessed MMR defects in Barrett-associated adenocarcinomas have reached different results. We therefore assessed the expression of the MMR proteins NILH1 and MSH2 in a series of 59 Barrett adenocarcinomas and found a loss of MMR protein immunostaining in 2/59 (3%) tumors; one tumor showed a loss of MSH2 expression, the other tumor showed a loss of MLH1, and both tumors displayed an NISI-high phenotype. Our findings suggest that only a small subset of Barrett adenocarcinomas develop because of defective MMR, but demonstrate that MLH1 and MSH2 are the primary targets for defective MMR also in this tumor type. (C) 2005 Elsevier Inc. All rights reserved.