Decreased expression of the peroxisomal bifunctional enzyme and carbonyl reductase in human hepatocellular carcinomas

Human hepatocellular carcinomas (HCC) are known to frequently exhibit clear -cell or fatty change. The expression of three enzymes related to fatty aci d metabolism, the peroxisomal bifunctional enzyme (enoyl-CoA hydratase/3-hy droxyacyl-CoA dehydrogenase, BE), cytosolic carbonyl reductase (CR) and the alpha-class glutathione S-transferase (GST) was investigated immunohistoch emically in 45 HCC samples, to examine their relevance to this phenomenon a nd to antioxidant cellular defence. The tumour sizes ranged from 3 mm to 37 mm in diameter (mean 19 mm). Of 8 highly differentiated carcinomas (Edmond son's grade I), 5 and 6 showed positive staining for BE and CR respectively , like the surrounding non-hepatoma tissues. Of 37 Edmondson's grade II-IV lesions, 31 exhibited negative or only weakly positive staining for both en zymes, as compared with the surrounding tissues. The combined rates for wea kly positive and negative staining for BE or CR were proportional to the de gree of dedifferentiation. However, 3 of 26 grade III tumours showed enhanc ed staining. Intensities of staining for CR were in accordance with those f or BE in 40 of the total of 45 HCC. Immunoblot analysis also demonstrated c oncerted alteration of the two enzymes in carcinoma tissues. The staining o f the alpha-class GST was hardly changed in Edmondson's grade I and II case s but was decreased in 24 of 31 grade III and IV lesions. The great majorit y of the BE-negative carcinomas did not demonstrate fatty or clear-cell cha nge. These results suggested that BE and CR might be possible markers for t he analysis of multistage hepatocarcinogenesis but that decrease or loss wa s not reflected in increased fat storage.