The potential role of bcl-2 mRNA and protein exression in hepatocellular carcinomas.
BACKGROUND
The bcl-2 gene regulates programmed cell death by providing a survival advantage to rapidly proliferating cells. In several malignant tumors bcl-2 presence has been associated with favorable prognosis. In the liver, bcl-2 is expressed in bile ductular cells and tumors of biliary origin. This study investigates the expression of bcl-2 mRNA and protein in hepatocellular carcinomas (HCC).


METHODS
The study comprised 35 primary HCC resected from 35 patients; 21 males and 14 females, aged from 43-59 years. The tumors were graded according to Edmondson criteria. In 28 cases HCC was developed on the background of cirrhotic liver. In 9 instances the patients received chemoembolization before surgery. The presence of bcl-2 mRNA was assessed on paraffin-embedded, 4 microm-thick sections, using a standard in situ hybridization method with a commercially available bcl-2 probe (Maxim Biotech, USA), while the streptavidin-biotin immunohistochemical technique was employed to detect bcl-2 protein expression using the monoclonal anti-bcl-2 antibody (DAKO, USA). The results were expressed as % of tumor-positive cells following morphometric analysis.


RESULTS
The in situ hybridization study revealed bcl-2 mRNA expression in 25 out of 35 (70%) HCC. In addition, bcl-2 mRNA was detected in hyperplastic cholangioles within fibrous septae in the periphery of the tumors. Immunohistochemical staining failed to reveal any bcl-2 protein expression in tumor cells of HCC, whereas hyperplastic cholangioles of the fibrous septae, in the periphery of the tumors and intratumoral lymphocytes displayed a strong-positive cytoplasmic (perinuclear) stain. No significant correlations were recorded between bcl-2 mRNA expression and tumor histological pattern, grade, stage and the use of previous chemoembolization.


CONCLUSIONS
In hepatocellular carcinomas, the bcl-2 gene is frequently present but its protein product is absent. This suggests a post-translational mechanism of bcl-2 protein degradation, indicating that bcl-2 does not play a substantial role in the progress of hepatocellular carcinoma.
Ravazoula
Panagiota
P
Department of Pathology, University of Patras School of Medicine, Greece.
Tsamandas
Athanassios C
AC
Kardamakis
Dimitrios
D
Gogos
Charalambos
C
Karatza
Chrisoula
C
Thomopoulos
Konstantinos
K
Tepetes
Konstantinos
K
Kourelis
Theodore
T
Petsas
Theodore
T
Bonikos
Dionissis S
DS
Karavias
Dionissios
D
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger