Combined loss of expression of O6-methylguanine-DNA methyltransferase and hMLH1 accelerates progression of hepatocellular carcinoma

BACKGROUND AND OBJECTIVES: O(6)-methylguanine-DNA methyltransferase (MGMT) and human Mut L homologue 1 (hMLH1) are proteins that play an important role in DNA repair. No reports have yet described whether deficient MGMT and hMLH1 expression correlates with tumor progression and the prognosis of patients with hepatocellular carcinoma (HCC). METHODS: Using immunohistochemical analysis, we evaluated the expression status of MGMT and hMLH1 protein in 60 paraffin-embedded samples from consecutive patients with curatively resected HCC. RESULTS: The lack of expression of both MGMT and hMLH1 in HCCs (n = 7) correlated with advanced pTNM stage (P = 0.039), as compared with HCCs expressing both proteins (n = 25). The absence of both MGMT and hMLH1 was a significant indicator of malignant potential. The expression status of both MGMT and hMLH1 was a predictive factor for overall survival in patients with HCC (P < 0.001). CONCLUSIONS: HCC lacking both MGMT and hMLH1 is correlated with an advanced stage and a poor prognosis. The expression status of both repair proteins is a predictive prognostic marker in patients with HCC after surgical resection.