Expression of mismatch repair proteins, hMLH1/hMSH2, in non-small cell lung cancer tissues and its clinical significance

Background: hMLH1 and hMSH2 have been implicated to be involved in the DNA mismatch repair (MMR) system. The purpose of this study is to investigate the expression of hMLH1 and hMSH2 DNA MMR proteins in non-small cell lung cancer (NSCLC) tissue and to elucidate their clinical significance. Methods: The hMLH1 and hMSH2 protein expression was evaluated by immunohistochemistry for a consecutive series of 113 NSCLC patients. The expressions of each protein were examined for an association with the clinicopathological variables, including genetic alterations analyzed by high resolution fluorescent microsatellite analysis. Results: Regarding the hMLH1 expression, the MSI-positive patients showed significantly lower scores than the MSI-negative patients. For hMSH2 expression, the patients with a 20 or higher pack-year index (PYI) showed significantly higher scores than the patients with a PYI less than 20. The expression status of proteins did not affect both the disease free and overall survival of the patients. No significant correlation was observed among the scores for the proteins. Conclusions: The expressions of hMLH1 and hMSH2 are independently regulated and play different roles in NSCLC. The genetic instability is possibly due to the reduced expression of hMLH1 protein, and hMSH2 expression is associated with smoking status.