Expression of c-MET Protein in Various Subtypes of Hepatocellular Adenoma Compared to Hepatocellular Carcinoma and Non-Neoplastic Liver in Human Tissue.

Hepatocellular adenoma (HA) is a benign neoplasm of the liver, whose aetiopathogenesis is little known. Newest research allowed dividing all cases into three types based on molecular characteristics: inflammatory HA, HA with HNF1A mutation, ß-catenin-mutated HA. The clinical significance of HA is chiefly due to the possibility of malignant transformation into hepatocellular carcinoma (HCC). The aim of the present study was to immunohistochemically assess the expression pattern and level of c-MET protein in hepatocellular adenoma (taking into account its status of Wnt/ß-catenin pathway functioning) and intertwining the results into a wider pattern of expression in non-neoplastic liver and hepatocellular carcinoma of various histological grades. It was found that expression of c-MET in poorly-differentiated HCC was significantly higher than in non-neoplastic liver and well- to moderately-differentiated HCC. The expression in HA was variable and differed between molecular subtypes of this neoplasm: inflammatory and HNF1A mutation-associated type are characterized by overexpression of c-MET to an extent comparable with poorly-differentiated HCC, whereas Wnt/ß-catenin dysfunction-associated type lacks overexpression, and the amount of c-MET protein accumulated in its cells is similar to the levels in non-neoplastic tissue and well- to moderately-differentiated HCC. These findings suggest that c-MET overexpression in HA is not an early event in hepatocarcinogenesis, but constitutes a divergent molecular pathway leading to neoplastic change compared to overexpression observed in the late stages of tumour progression.

Comparison of Subtypes of Hepatocellular Adenoma to Hepatocellular Carcinoma and Non-Neoplastic Liver Tissue in Terms of PTEN Expression.

PTEN is a tumour suppressor gene whose loss of function has been found to be present in a variety of neoplasms, both benign and malignant. In hepatocellular carcinoma (HCC), loss of PTEN is associated with poorly differentiated cancer, advanced clinical stage and tendency to recur. The extent and meaning of PTEN loss in hepatocellular adenoma (HA), one of the precursor lesions for HCC, has not yet been analysed. The aim of the present study was to evaluate the possible loss of PTEN expression in HA in the wider context of hepatocarcinogenesis. Immunohistochemical analysis of PTEN expression was performed in non-neoplastic liver tissue, HAs and HCCs. It has been found that the loss of PTEN was markedly present in poorly differentiated HCC, whereas well to moderately differentiated HCC showed similar levels of PTEN expression to nonneoplastic liver. HAs presented as a heterogeneous group, with loss of PTEN observed in the inflammatory and HNF1A-mutated subtype and relatively intact PTEN expression in HA with nuclear ß-catenin overexpression. This suggests that the loss of PTEN might occur both in HA and HCC, constituting different outcomes of the same molecular lesion in the various contexts of malignant or benign neoplasms.