Expression of xenobiotic and steroid hormone metabolizing enzymes in hepatocellular tumors of the non-cirrhotic liver.

ABSTRACT

Hepatocellular adenomas (HCA) and some hepatocellular carcinomas (HCC) arise in the non-cirrhotic liver. Although the liver is involved in the metabolism of a huge number of exogenous and endogenous substances, little is known about the role of metabolic enzymes in the development of liver tumors in the absence of cirrhosis. We analyzed the expression of glutathione S-transferases (GST) and cytochrome P450 enzymes (CYP) in 23 HCA, 20 HCC, and 22 focal nodular hyperplasias (FNH) using immunohistochemistry. The liver tissue revealed consistent specific staining for GST alpha, CYP1A1, 1A2, 2E1, and 3A4. In HCA and HCC, GST alpha expression was significantly reduced (p<0.001 and 0.043). Reduced GST alpha expression was significantly associated with steatosis in HCA and HCC (n=12, p=0.006), but not in non-neoplastic liver tissue. CYP3A4 expression was also reduced in HCA and HCC (p=0.03 and 0.02), and this was correlated with diabetes mellitus type 2 (p=0.02). In conclusion, HCA and HCC revealed changes in the expression of certain metabolic enzymes as compared with the non-neoplastic liver tissue or FNH. Therefore, reduced expression of GST alpha and CYP3A4 may indicate specific metabolic defects in the tumor tissue characterizing subgroups of HCA and HCC.