Expression of hMSH2 and hMLH1 in colorectal carcinomas with microsatellite instability.
Microsatellite instability (MIN) due to defective mismatch repair (MMR) genes has been reported in a subset of sporadic colorectal carcinomas and in the majority of tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. Among the known MMR genes, hMSH2 and hMLH1 genes are known to be predominantly altered in HNPCC patients and MIN-positive tumors. In this study, we examined MIN and the protein expression pattern of the hMSH2 and hMLH1 by Western blot and immunohistochemistry from 32 sporadic colorectal carcinomas. MIN was observed in 6 (18%) colorectal carcinomas. Of the 6 MIN-positive tumors, one case showed no expression of either protein, 3 cases showed an absence of hMSH2 protein expression, one case showed an absence of hMLH1 protein expression and one case showed no altered expression of either protein by immunohistochemistry. The decreased expression of the hMSH2 protein in a tumor compared to the normal mucosa was also observed in 5 of the 6 MIN-positive cases by Western blot analysis. All of the MIN-negative tumors showed expression of both proteins by immunohistochemistry. Thus most of the MIN-positive tumors appear to be directly related to the altered expression of these two genes and can be diagnosed by the examination of protein expression.
Kim
H
H
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea. gohk@bora.dacom.co.kr
Piao
Z
Z
Kim
J W
JW
Choi
J S
JS
Kim
N K
NK
Lee
J M
JM
Park
J H
JH
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein