DIFFERENT EXPRESSION OF PI3K/AKT/MTOR PROTEINS ACCORDING TO THE CHRONIC LIVER DISEASE ETIOLOGY IN HEPATOCELLULAR CARCINOMA

Introduction: Chronic liver disease (CLD) of different etiologies leads to hepatocellular carcinoma (HCC) by multiple mechanisms that may be translated into clinicopathological and prognostic differences. Objective: This study aimed to evaluate the tissue expression of the PBK/Akt/mTOR pathway proteins, important signalling cascades in HCC, and their association with long-term outcome and other parameters, according to the etiology of the CLD, in HCC patients. Methods: Clinic and histopathological data from 80 patients who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were compared according to CLD etiology. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analyzed. Pathway protein expression was assessed by immunohistochemistry (IHQ) in both tumor and underlying cirrhosis and by RT-PCR in tumor tissue. Results: There were 41 patients of viral (V) (Hepatis B or C virus infection HBV or HCV) and 39 of nonviral (NV) (alcohol abuse and cryptogenic) etiology. Etiologic groups were similar regarding laboratory and clinicopathological indices. Strong expression (SE) of PI3K, but not for AKT and mTOR, was more frequent in tumors arising from viral and nov-viral group of liver disease than cirrhotic parenchyma (respectively 35.9×11.1%, p=0.04; and 53.8×24.2%, p=<0.01), without differences in its tumor expression between the etiologic groups (p=0.111). mRNA of PI3K were expressed in tumor, without differences between CLD etiologies, neither association with IHQ findings. Older age and microvascular invasion (MIV) were the only parameters independently associated with event. MIV was also associated with shorter EFS. Conclusions: PI3K could have a role on hepatocarcinogenesis, given that its strong expression was more frequent in tumor than in cirrhosis. However, as differences regarding clinical outcome between etiologic groups of CLD in HCC patients were not demonstrated, the prognostic and therapeutic implications need to be further investigated.