[Expression of hMSH2 and hMLH1 in stomach cancer and their correlation with Helicobacter pylori infection].
OBJECTIVE
The carcinogenesis of gastric carcinoma is related to many factors. Helicobacter pylori (HP) infection is one of the factors causing gastric carcinoma, but the exact molecular mechanism is not clear. Mismatch repair genes are important in keeping the accuracy of DNA replication. They are associated with carcinogenesis of alimentary canal. In order to investigate the role of hMSH2 and hMLH1 in stomach cancer and the possible mechanism of carcinogenesis caused by HP infection, we tested cancer tissue, surrounding mucosa and chronic superficial gastritic mucosa with and without HP infection.


METHODS
HP infection was determined with quick-ureolytase method. Immunohistochemistry staining was used to exam the expression of hMSH2 and hMLH1 in tumor tissue and their surrounding mucosa and gastric mucosa. Chi-square was used for statistic analysis.


RESULTS
The positive rate (67.1%) of hMSH2 expression in cancer tissue was significantly higher than those of surrounding mucosa (35.5%) and gastritic mucosa (42.1%) (P< 0.05); the positive rate (81.1%) of hMSH2 expression in poor differentiation group was significantly higher than those in well middle differentiation group (54.5%) and mucoid carcinoma group (54.5%) (P< 0.05), but there was no significant difference between the latter two groups. There was no significant difference among the positive rates of hMLH1 expression in cancer tissue (81.6%), in surrounding mucosa (90.8%), and in gastritic mucosa (89.5%) (P>0.05). The positive rate (47.1%) of hMLH1 expression in mucoid carcinoma group was significantly higher than those in well middle differentiation group (81.8%) and poor differentiation group (97.3%) (P< 0.05), but there was no significant difference between the latter two groups (P>0.05). In cancer tissue, the positive rate (56.8%) of hMSH2 expression in HP infection group was significantly lower than that without HP infection group (81.3%) (P< 0.05); the positive rates of hMLH1 expression was 77.2% in HP infection group and 87.5% in without HP infection group, but there was no significant difference between two groups (P >0.05). In surrounding mucosa, the positive rate of hMSH2 expression was 29.5% in HP infection group and 43.8% in without HP infection group, as well as those of hMLH1 were 86.4% and 96.9%, there were no significant differences between the groups. In gastritic mucosa, the positive rate of hMSH2 expression was 38.5% in HP infection group and 50.5% in HP-negative group, as well as those of hMLH1 were 88.5% and 91.7%; there was no significant difference between the groups.


CONCLUSIONS
The expression of hMSH2 is associated with carcinogenesis of stomach cancer, and its high expression may be a potential marker of stomach cancer; HP infection inducing low expression of hMSH2 and hMLH1 may be one of molecular mechanisms by which HP infection leads to stomach cancer.
Ma
Jian-Mei
JM
Molecular Biology Laboratory, The Second Affiliated Hospital of Dalian Medical University, Liaoning, 116027, PR China. jianmeima@hotmail.com
Wang
Zhao-Hui
ZH
Liu
Min
M
Wang
Mei
M
Zhang
Yan
Y
Lu
Shen
S
Liu
Li-Na
LN
Xu
Guo-Wang
GW
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000378:metabolism / Q000382:microbiology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000382:microbiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; 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