Metastatic tumor antigen 1 is closely associated with frequent postoperative recurrence and poor survival in patients with hepatocellular carcinoma

Abstract

Metastatic tumor antigen 1 (MTA1) is known to play a role in angiogenic processes as a stabilizer of hypoxia‐inducible factor 1‐α (HIF1‐α). In this study, we examined whether overexpression of MTA1 affects the recurrence of hepatocellular carcinoma (HCC) after surgical resection and the survival of the patients. A total of 506 HCC patients who underwent hepatic resection were included in the study. They were followed up for a median of 43 months (range, 1‐96 months) after hepatectomy. MTA1 expression levels were determined by the proportion of immunopositive cells (none, all negative; +, 50%). The relationships between MTA1 expression and the HCC histological features, the appearance of recurrent HCC after surgical resection, and the survival of the patients were examined. Eighty‐eight cases (17%) of the HCCs were positive for MTA1, although the surrounding liver tissues were all negative for MTA1; 62 cases were + and 26 cases were ++. Increased MTA1 expression levels in HCC were correlated with larger tumors (P = 0.04), perinodal extension (P = 0.03), and microvascular invasion (P = 0.008). Histological differentiation had marginal significance (P = 0.056). However, there was no association between MTA1 expression and age, sex, Child‐Pugh class, and capsule invasion of HCC. Interestingly, MTA1 expression levels were significantly greater in hepatitis B virus (HBV)‐associated HCC compared with hepatitis C virus (HCV)‐associated HCC (P = 0.017). The cumulative recurrence rates of MTA1‐positive HCCs were markedly greater than those of MTA1‐negative HCCs (P < 0.0001). The cumulative survival rates of patients with MTA1‐positive HCCs were significantly shorter than those of patients with MTA1‐negative HCCs (P < 0.0001). In conclusion, our data indicate that MTA1 is closely associated with microvascular invasion, frequent postoperative recurrence, and poor survival of HCC patients, especially in those with HBV‐associated HCC. (HEPATOLOGY 2008;47:929–936.)