Clinicopathological Correlation of hMLH1 and hMSH2 Protein Expressions in Stage III Colon Cancer

ABSTRACT

PURPOSE: Functional loss of mismatch repair has been reported to be the reason for resistance to several chemotherapeutic drugs. The expressions of hMLH1 and hMSH2 were examined to assess whether they correlated with the biological behavior and the chemotherapeutic responsiveness in paflents with sporadic colon cancers. METHODS: Ninety-one patients with stage III primary colon cancer were included from the tumor registry of the Asan Medical Center, Seoul, Korea. All patients underwent a curative operation and postoperative chemotherapy with 5- fluorouracil and leucovorin for 6 cycles between 1993 and 1997. Immunohistochemical staining for hMLH1 and hMSH2 was performed using archival paraffin blocks. A positive expression was determined when unequivocal nuclear staining was identified in more than 10% of the cancer cells. The survival and the clinicopathologic variables regarding hMLH1 and hMSH2 expressions were assessed using the log-rank test and the Cox proportional regression method. RESULTS: Either hMLH1 or hMSH2 expression was lost in nine cases (9.9%). hMLH1 and hMSH2 expressions were significantly correlated with tumor invasion (P=0.012) and tumor differentiation (P=0.017). The disease-free survival did not differ with respect to hMLH1 and hMSH2 expressions. The number of metastatic lymph nodes and the preoperative serum CEA level were independent predictors of disease-free survival on a multivariate analysis. CONCLUSIONS: The loss of hMLH1 or hMSH2 expresscon appears to be involved in the differentiation of and the invasion by colon cancer. However, nether hMLH1 nor hMSH2 expression was correlated withthe 5-fluorouracil responsiveness.