title: Detection of chromosomal aberrations in well-differentiated hepatocellular carcinoma by bright-field in situ hybridization.
abstract: Differentiation between well-differentiated hepatocellular carcinoma (HCC) and nonmalignant lesions with increased cellular proliferation may be difficult in needle biopsies. Based on recurrent chromosome aberrations known for HCC, we developed a nonfluorescent in situ hybridization technique that allows combination with morphological analysis in bright-field microscopy. Fourteen biopsies of HCC and 31 samples of regenerative nodules (n = 10), chronic hepatitis (n = 10), fibrosis or cirrhosis of unknown origin (n = 5), focal nodular hyperplasia (n = 2), primary biliary cirrhosis (n = 2), steatosis (n = 1), and adenomatous hyperplasia (n = 1) were analyzed with probes specific for the centromeric regions of chromosomes 1, 6, 7, and 8. After microwave pretreatment and in situ hybridization, signals were detected using a tyramine-based system and AEC as substrate. Evaluation of signals was done by conventional bright-field microscopy. Using this approach, aberrant counts were seen for at least one chromosome in 12/14 cases of HCC. In contrast, none of the nonmalignant lesions revealed aberrant counts for any of the chromosomes analyzed. In conclusion, this new combination of in situ hybridization and tyramine amplification allows fast and reliable evaluation of chromosome aberrations in a histomorphological context similar to paraffin immunohistochemistry. Registration of imbalances contributes to a reliable differentiation between malignant and nonmalignant lesions of the liver.
authors.affiliation: Department of Pathology, Medizinische Hochschule, Hannover, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wilkens
authors.forename: Martin
authors.initials: M
authors.lastname: Bredt
authors.forename: Antje
authors.initials: A
authors.lastname: Flemming
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Juergen
authors.initials: J
authors.lastname: Klempnauer
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Peer
authors.initials: P
authors.lastname: Flemming
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged