title: The potential role of bcl-2 mRNA and protein exression in hepatocellular carcinomas.
abstract: 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.
authors.affiliation: Department of Pathology, University of Patras School of Medicine, Greece.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Ravazoula
authors.forename: Athanassios C
authors.initials: AC
authors.lastname: Tsamandas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kardamakis
authors.forename: Charalambos
authors.initials: C
authors.lastname: Gogos
authors.forename: Chrisoula
authors.initials: C
authors.lastname: Karatza
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Thomopoulos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tepetes
authors.forename: Theodore
authors.initials: T
authors.lastname: Kourelis
authors.forename: Theodore
authors.initials: T
authors.lastname: Petsas
authors.forename: Dionissis S
authors.initials: DS
authors.lastname: Bonikos
authors.forename: Dionissios
authors.initials: D
authors.lastname: Karavias
mesh_terms: 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
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger