Correlation between hMLH1/hMSH2 and p53 protein expression in sporadic colorectal cancer.
OBJECTIVE
The aim of this study was to analyze expression of hMLH1 and hMSH2 mismatch repair proteins in terms of p53 protein expression and clinicopathological parameters in sporadic colorectal cancer.


METHODS
Four hundred and two cases of curative colorectal surgery for primary colorectal cancer were included in this study (patients with a familial history of colorectal cancer and familial adenomatous polyposis were not included). Clinicopathological parameters were reviewed retrospectively. HMLH1, hMSH2 and p53 protein expression in tumor tissue sections was determined using immunohistochemical staining with specific monoclonal antibodies.


RESULTS
Of the 402 cases, immunohistochemical analysis showed 35 (8.7%) had loss of expression of hMLH1, 19 (4.7%) had loss of expression of hMSH2, and three cases (0.7%) had loss of expression of both proteins. Multivariate analysis showed that early age of onset (p=0.023), right side dominance (p<0.001) and poorly differentiated or mucinous cell type (p<0.001) were associated with loss of expression of hMLH1 or hMSH2. Loss of expression of hMLH1 or hMSH2 correlated with low p53 expression (p<0.001). In terms of clinicopathological parameters, p53 expression was associated only with hMLH1 or hMSH2 expression.


CONCLUSIONS
Colorectal cancers not expressing hMLH1 or hMSH2 may have distinct features from those expressing these mismatch repair proteins. p53 expression appears to be implicated in a compensatory pathway with mismatch repair proteins.
Park
In J
IJ
Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center Seoul, Korea.
Kim
Hee C
HC
Kim
Jung S
JS
Yu
Eun S
ES
Yu
Chang S
CS
Kim
Jin C
JC
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013194:Staining and Labeling; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein