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Expression and Prognostic Significance ofO⁶-Methylguanine-DNA Methyltransferase in Hepatocellular, Gastric, and Breast Cancers

From the Departments of Surgery (SM, KM, HY) and Pathology (AO), Saga Medical School, Saga, Japan; Department of Orthopedic Surgery (KH), Faculty of Medicine, Kyushu University, Fukuoka, Japan; Department of Biochemistry (YN), Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Japan Science and Technology Corporation (YN), Japan; and Department of Biology and Frontier Research Center (MS), Fukuoka Dental College, Fukuoka, Japan.

Correspondence: Address correspondence and reprint requests to: Kohji Miyazaki, MD, PhD, Department of Surgery, Saga Medical School, 5-1-1, Nabeshima, Saga 849-8501, Japan; Fax: 81-952-34-2019.

Background: O⁶-Methylguanine-DNA methyltransferase (MGMT) is an enzyme that repairs O⁶-methylguanine, a promutagenic DNA base damaged by endogenous and environmental alkylating agents. There are few reports that describe whether or not abnormal MGMT expression correlates with the prognosis in human solid cancers.

Methods: The expression of MGMT was immunohistochemically evaluated in 60, 62, 105, and 46 paraffin-embedded samples from patients with curatively resected hepatocellular, gastric, colorectal, and breast cancers, respectively.

Results: The expression of MGMT was a positive predictive factor for overall survival in hepatocellular (P = .005) and gastric cancers (P < .001) and for relapse-free survival in breast cancers (P < .001). MGMT-positive gastric tumors (n = 42) were correlated with the absence of serosal invasion (P = .045), lymph node metastasis (P = .006), intestinal type (P = .018), and low pathological tumor, node, metastasis stage (P < .001). All breast tumors that recurred locally after operation were MGMT negative (P = .004). The clinicopathologic characteristics of colorectal cancers with respect to MGMT expression did not significantly differ.

Conclusions: The expression of MGMT is a predictive prognostic marker in patients with hepatocellular, gastric, and breast cancers. These findings may help to establish therapeutic strategies for patients with these types of solid cancer.

Key Words: O⁶-methylguanine-DNA methyltransferase (MGMT) • Hepatocellular carcinoma • Gastric cancer • Colorectal cancer • Breast cancer • Prognosis

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