Akt, a down-stream target of phosphatidylinositol-3 kinase, plays multiple roles in carcinogenesis. To elucidate its role in hepatocarcinogenesis, we immunohistochemically investigated the expression of Akt protein (Akt1 and Akt2) in tumor and non-tumor tissues from 56 patients with hepatocellular carcinoma (HCC). High expression of Akt2 in HCC tissues was detected in 21 cases (38%) while Akt1 expression was moderate or less in all cases. Low expression of Akt2 was associated with histopathological differentiation, portal invasion and number of tumor nodules (p=0.026, 0.023, and 0.001, respectively). Univariate analysis showed that Akt2, histopathological differentiation, and portal vein invasion were significant prognostic factors (p=0.001, 0.028, and 0.006, respectively). Multivariate analysis revealed that in addition to histopathological differentiation, Akt2 was an independent prognostic marker (risk ratio for cancer relapse, 6.35, p=0.012). In contrast, Akt1 expression did not correlate with any clinicopathological features. Our findings suggest that Akt2, but not Akt1, is a novel independent predictor for the development and progression of HCC.

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