Mismatch pair defective phenotype in hereditary nonpolyposis colorectal cancer in the Chinese
Cai, Q.; Sun, M-hong.; Lu, H-fen.; Xu, X-li.; Min, D-liu.; Zhang, T-ming.; Shi, D-ren.
Zhonghua Zhong Liu Za Zhi 25(5): 420-424
2003
ISSN/ISBN: 0253-3766 PMID: 14575560 Document Number: 554905
Objective: To study the protein expression pattern of DNA mismatch repair genes hMSH2, hMLH1 and the microsatellite instability (MSI) status in the tumor tissue from hereditary nonpolyposis colorectal cancer in the Chinese. Methods: Fifty-eight families fulfilling different clinical criteria including Amsterdam Criteria (AC) (22/24 families, 38 tumors), Japanese Criteria (JC) (12/15 families, 16 tumors) and Bethesda Guidelines (BG) (12/19 patients, 13 tumors) were studied. Monoclonal antibodies against hMSH2, hMLH1 proteins and a panel of microsatellite markers (5 loci) including BAT26, BAT25, D2S123, D5S346 and D17S250 were used for study. Results: MSI-H was identified in all 22 (100%) AC tumors, with 81.8% (18/22) showing altered hMSH2 or hMLH1 expression; in 14/15 (93.8%) JC cancer, 1/1 (100%) JC adenoma, with 45.5% (5/11) showing altered hMSH2 or hMLH1 expression; and in 7/13 (53.8%) BG tumors, with 4/7 showing loss of hMSH2 or hMLH1 gene expression. Conclusion: The frequency of MSI-H and loss of mismatch repair protein are different in the families fulfilling different clinical criteria. Amsterdam Criteria and Japanese Criteria are the two most useful criterion systems for identifying mismatched repair defective tumors. However, Bethesda Guidelines should also be used for detecting more such tumors. The combination of immunohistochemical methods and microsatellite instability analysis is an effective strategy to detect the mismatch repair defective tumors. A close correlation does exist between hMSH2, hMLH1 protein expression pattern and MSI status.