High levels of BCL-2 messenger RNA detected by in situ hybridization in human hepatocellular and cholangiocellular carcinomas

Immunocytochemistry has indicated that, in the liver, the bcl-2 gene is gen erally expressed in bile duct cells and turners of biliary origin. Both in situ hybridization and immunocytochemistry were used to analyze the express ion of bcl-2 messenger RNA (mRNA) and its protein product (Bcl-2) in the ti ssue of 50 pure primary liver tumor (PLT) specimens including 40 hepatocell ular carcinoma (HCC) specimens and 10 cholangiocellular carcinoma (CC) spec imens. The phenotype of the tumors expressing bcl-2 was confirmed by immuno cytochemical assessment of the cytokeratin (CK) profile (CK8, CK18, CK7, an d CK19). Whereas positive immunoreaction with the anti-Bcl-2 MoAb was revea led in only 8 (20%) of 40 HCC specimens and 1 (10%) of 10 CC specimens, hig h contents of bcl-2 mRNA were found in 26 (65%) of 40 HCC specimens and 9 ( 90%) of 10 CC specimens. Regarding the CK profile, only 25 (62%) of 40 HCC specimens showed pure hepatocytic lineage (CKs 8-18), whereas among the rem aining 15 HCC specimens, positivity for either CK7 (12 specimens) or CK19 ( 5 specimens) was observed. All 10 CC specimens stained with CKs 8-18-19, an d 8 of 10 stained with CK 7 as well. These results indicate that PLTs displ ay a greater expression of bcl-2 mRNA than of the Bcl-2 protein. Furthermor e, CK profile assessment confirmed that bcl-2 expression is not confined to liver tumors of biliary origin. In the absence of a well-demonstrated post transcriptional control of the gene, the authors propose the detection of b cl-2 mRNA by in situ hybridization as a possible alternative method for ass essing the expression of bcl-2 mRNA in PLT.