CONTEXT: Microsatellite instability (MSI) due to defective mismatch repair (MMR) genes has been reported in the majority of colorectal tumors from patients with hereditary nonpolyposis colorectal cancer syndrome and in 10% to 15% of sporadic colorectal cancers. The identification of cancers associated with MSI requires classical molecular testing as the gold standard. OBJECTIVE: The aim of this study was to evaluate the role of immunohistochemistry with antibodies directed against 4 MMR proteins as a screening tool for carcinomas with MSI. METHODS: In this study, 204 formalin-fixed, paraffin-embedded colorectal carcinomas were examined for MMR protein expression (hMLH1, hMSH2, hMSH6, and hPMS2) and analyzed for MSI (MSI-H indicates at least 2 of 6 markers affected). These results were correlated with histopathologic parameters. RESULTS: Immunohistochemical analysis revealed that loss of expression of at least 1 protein was present in 17% of cases. One hundred percent of carcinomas that showed high instability (MSI-H) showed loss of expression of hMLH1, hMSH2, or hMSH6. Loss of expression of 2 proteins was present in 59.4% of MSI-H cases, with only 2 combinations, namely, hMLH1/hPMS2 and hMSH2/hMSH6. Isolated loss of hMSH6 expression was present in 2 MSI-H cases. CONCLUSIONS: These findings confirm that examination of MMR protein expression by immunohistochemistry is a simple method to diagnose colorectal cancer with MSI. Our data suggest that the study of hMSH6 may be useful, in addition to hMLH1 and hMSH2. Moreover, immunohistochemistry could represent a screening method with which to direct research on the mutations of MMR genes observed in hereditary nonpolyposis colorectal cancer syndrome.
CONTEXT: Microsatellite instability (MSI) due to defective mismatch repair (MMR) genes has been reported in the majority of colorectal tumors from patients with hereditary nonpolyposis colorectal cancer syndrome and in 10% to 15% of sporadic colorectal cancers. The identification of cancers associated with MSI requires classical molecular testing as the gold standard. OBJECTIVE: The aim of this study was to evaluate the role of immunohistochemistry with antibodies directed against 4 MMR proteins as a screening tool for carcinomas with MSI. METHODS: In this study, 204 formalin-fixed, paraffin-embedded colorectal carcinomas were examined for MMR protein expression (hMLH1, hMSH2, hMSH6, and hPMS2) and analyzed for MSI (MSI-H indicates at least 2 of 6 markers affected). These results were correlated with histopathologic parameters. RESULTS: Immunohistochemical analysis revealed that loss of expression of at least 1 protein was present in 17% of cases. One hundred percent of carcinomas that showed high instability (MSI-H) showed loss of expression of hMLH1, hMSH2, or hMSH6. Loss of expression of 2 proteins was present in 59.4% of MSI-H cases, with only 2 combinations, namely, hMLH1/hPMS2 and hMSH2/hMSH6. Isolated loss of hMSH6 expression was present in 2 MSI-H cases. CONCLUSIONS: These findings confirm that examination of MMR protein expression by immunohistochemistry is a simple method to diagnose colorectal cancer with MSI. Our data suggest that the study of hMSH6 may be useful, in addition to hMLH1 and hMSH2. Moreover, immunohistochemistry could represent a screening method with which to direct research on the mutations of MMR genes observed in hereditary nonpolyposis colorectal cancer syndrome.
Authors: Dominik Alexander; Nirag Jhala; Chakrapani Chatla; Jon Steinhauer; Ellen Funkhouser; Christopher S Coffey; William E Grizzle; Upender Manne Journal: Cancer Date: 2005-05-15 Impact factor: 6.860
Authors: P Cuilliere-Dartigues; B Fabiani; S Dumont; C Copie-Bergman; A Couvelard; T Molina; A Duval; J F Flejou Journal: Virchows Arch Date: 2007-09-12 Impact factor: 4.064
Authors: Annegret Müller; Dirk Zielinski; Nicolaus Friedrichs; Barbara Oberschmid; Sabine Merkelbach-Bruse; Hans K Schackert; Markus Linnebacher; Magnus von Knebel Doeberitz; Reinhard Büttner; Josef Rüschoff Journal: Virchows Arch Date: 2008-06-26 Impact factor: 4.064