Immunohistochemical analysis of pro-apoptotic Bid level in chronic hepatitis, hepatocellular carcinoma and liver metastases

Bid, a member of the Bcl-2 family, mediates apoptosis by inducing the relea se of proapoptotic factors. The expression of Bid in liver diseases has not been investigated. This study evaluated Bid level in various liver disease s including hepatocellular carcinoma (HCC), liver metastases from colorecta l cancer, chronic hepatitis and liver cirrhosis. The expression of Bid in t umorous tissues of HCC was lower than that in their corresponding non-tumor ous tissues from the same patient. Heavy staining with Bid antibody was fou nd in some localized tumorous liver tissues from patients with poorly diffe rentiated tumors. In patients with chronic hepatitis and liver cirrhosis, t here were gradient tumor-development centers, a gradient increase in reacti on with Bid antibody from the middle of the center to its edge. The gradien t tumor-development center was also found in non-tumorous tissues of HCC, s uggesting that occurrence of this center in chronic hepatitis might be an e arly pathologic sign of HCC development. Bid was also expressed in the epit helial cells in tissues from liver metastases and their expression was ofte n stronger than in the non-tumorous liver tissues. Heavy nuclear staining o f Bid was not uncommon in these metastatic cells. The different patterns of staining between primary and secondary liver tumors may reflect a differen ce in tumor origin and in cell type. Nuclei of metastatic cells, though pos itive for Bid, still showed a considerable mitotic activity, indicating tha t they were in active proliferation rather than on a pathway deemed to be a poptotic. In conclusion, this study shows that the Bid level is decreased i n HCC except in poorly differentiated HCC in which cells may undergo a proc ess of apoptosis or necrosis. The existence of gradient tumor-development c enter in chronic hepatitis, liver cirrhosis and nontumorous tissues from HC C may serve as a pathologic marker of a carcinogenic change of cell phenoty pes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.