1. ¹Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden
2. ²Department of Pathology and Cytology, Karolinska Institute, Stockholm, Sweden
3. ³Department of Pathology, Charite University Clinic, Berlin, Germany

Correspondence: Dr. Annika Lindblom, Department of Molecular Medicine, Karolinska Institute, L8:02, S-17176 Stockholm, Sweden. E-mail: annika.lindblom@cmm.ki.se

Received 7 December 2000.

Abstract

Immunohistochemical expression analysis of mismatch repair gene products has been suggested for the prediction of hereditary nonpolyposis colorectal cancer (HNPCC) carrier status in cancer families and the selection of microsatellite instability (MSI)-positive tumors in sporadic colorectal cancer. In this study, we aimed to evaluate hMSH2 and hMLH1 immunohistochemistry in familial and sporadic colorectal cancer. We found that immunohistochemistry allowed us to identify patients with germline mutations in hMSH2 and many cases with germline mutations in hMLH1. However, some missense and truncating mutations may be missed. In addition, hMLH1 promoter methylation, commonly occurring in familial and sporadic MSI-positive colorectal cancer, can complicate the interpretation of immunohistochemical expression analyses. Our results suggest that immunohistochemistry cannot replace testing for MSI to predict HNPCC carrier status or identify MSI-positive sporadic colorectal cancer.