Expression of hMLH1 and hMSH2 Proteins in Non-Small Cell Lung Cancer and Its Clinicopathologic Significance – From the Viewpoint of Forthcoming New TNM Classification
JY Choe, KB Lee, HJ Lee, XH Xu, JH Chung. Seoul National University Bundang Hospital, Seongnam, Korea; Seoul National University College of Medicine, Seoul, Korea
Background: The inactivation of mismatch repair (MMR) system is one of the important mechanisms in the carcinogenesis of colon cancer. But in non-small cell lung cancer (NSCLC), it is not fully studied although microsatellite instability (MSI) which is resulted from loss of MMR system reported up to 68%. Moreover its clinicopathologic significance seems to be controversial. Thus we investigate the expression of DNA MMR proteins, hMLH1 and hMSH2 in NSCLC and evaluate their clinicopathologic significance. Pathological stages were compared between present TNM stage and forthcoming new TNM stage proposed by the International Association for the Study of Lung Cancer (IASLC).
Design: Consecutive 293 cases of surgically resected NSCLC specimen were enrolled in this study. Immunohistochemical analysis for hMLH1 and hMSH2 were performed and correlated with the clinicopathological characteristics. Statiscal analyses were performed using the χ² analysis and the Kaplan-Meier method.
Results: The frequency of loss of hMLH1 and hMSH2 proteins were 27.6% (79/286) and 8.7% (25/288), respectively. Loss of MMR proteins were correlated with present and new TNM stage classification. Loss of hMLH1 was correlated with newly revised TNM stage (p=0.043) as well as old TNM stage (p=0.031) including T stage (p=0.047) and N stage (p=0.037). Furthermore in hMSH2, it was more closely correlated with proposed TNM stage (p=0.001) similar to present TNM stage (p=0.001) including T stage (p=0.003) and N stage (p=0.006). Also, expression of hMSH2 tended to be associated with disease free survival (p=0.073).
Conclusions: Less correlation in hMLH1 compared to hMSH2 may be explained by differences of the mechanism of the inactivation of MMR system. There were no significant differences between loss of MMR proteins and other clinicopathologic factors. In conclusion, the inactivity of MMR system is correlated with advanced TNM stage in both current and proposed TNM system, more prominent in hMSH2. This is the largest study to show correlation between loss of MMR proteins and poor prognosis in the NSCLC.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 262, Tuesday Morning