Immunohistochemical Expression of Components of the Akt-mTORC1 Pathway is Associated with Hepatocellular Carcinoma in Patients with Chronic Liver Disease

Activation of the Akt-mTORC1 signaling pathway was evaluated in premalignant and hepatocellular carcinoma (HCC) lesions by assessing the expression of pS6, an Akt effector, and PTEN, an Akt suppressor. Methods: Immunohistochemical staining for pS6 and PTEN was performed on liver tissue from 52 patients with cirrhosis, with and without HCC. Two pathologists independently evaluated pS6 staining on a semiquantitative scale and categorized PTEN staining as present or absent. Results: In the HCC group, pS6 staining was greatest in HCC, followed by dysplasia, and benign cirrhotic tissue (P < 0.001). pS6 staining was greater in cirrhotic tissue from patients with HCC compared to cirrhosis in patients without HCC (P = 0.03). PTEN staining in tumor was absent in 8/33 (24%) cases. Loss of PTEN expression was more common in patients with higher tumor stage, compared to those with stage 1 tumors (P = 0.04). Conclusion: Immunohistochemical evidence of activation of the Akt-mTORC1 pathway is associated with HCC.