The role of expression of mismatch repair proteins hMSH2 and hMLH1 in gastric carcinogenesis and its clinical significance

Objective To investigate the expression of the mismatch repair proteins hMSH2 and hMLH1, and to examine the clinical significance of the intracellular expression site (ICES) in gastric carcinogenesis. Methods Specimens from 172 cases of gastric cancer, 151 tissues from paraneoplastic gastric mucosa and 34 from noncancerous gastric mucosa were collected in Dalain, China. An immunohistochemical method was used to determine the expression of the hMSH2, hMLH1 proteins and their ICES in the gastric mucosas. Results The rate of hMSH2 expression in gastric cancers, paraneoplastic gastric mucosas and noncancerous gastric mucosas were respectively 69.8%, 49.7% and 32.4%. The rate was significantly higher in gastric cancer compared to the latter two groups ( P =0.000), but there was no obvious difference in the expression between the two latter groups ( P =0.067). The hMLH1 protein expression rates were respectively 73.3%, 57.6% and 41.2% in the above three groups. The expression was significantly higher in the gastric cancer group compared to the two latter groups ( P =0.000), while there was no significant difference between the latter groups ( P =0.082). There was no obvious correlation between the hMSH2 and hMLH1 protein expression rates and related factors, such as gender, age and differentiated level of gastric cancer etc. The cell-nuclear expression of the hMSH2 protein was respectively 70.0%, 58.7% and 36.4% in the gastric cancer, paraneoplastic gastric mucosa and noncancerous gastric mucosa groups. The cytoplasmic expression rates were 30.0%, 41.3% and 63.6% in the three groups. The cell-nuclear expression rate of the hMSH2 protein gradually decreased in the gastric mucosas in the following order: cancer, paraneoplastic and noncancerous but cytoplasmic expression only increased slightly in these groups ( r =0.161, P =0.020). There was no significant difference in the ICES of the hMLH1 protein among the three different gastric mucosas ( P =0.659). Conclusion Simultaneous determination of the expression and ICES of the mismatch repair proteins hMSH2 and hMLH1 in the gastric mucosa may be helpful in detecting early gastric cancer.