title: Chromogenic in situ hybridization analysis of Epidermal Growth Factor Receptor gene/chromosome 7 numerical aberrations in hepatocellular carcinoma based on tissue microarrays.
abstract: Although Epidermal Growth Factor Receptor (EGFR) overexpression is observed frequently in hepatocellular carcinomas (HCC), specific gene deregulation mechanisms remain unknown. Our aim was to investigate the prognostic significance of the combined protein and gene/chromosome 7 numerical alterations. Using tissue microarray technology, thirty-five (n = 35) paraffin embedded histologically confirmed HCCs were cored and re-embedded in a paraffin block. Immunohistochemistry was performed for the determination of EGFR protein levels and evaluated by the performance of digital image analysis. Chromogenic in situ hybridization was also performed based on the use of EGFR gene and chromosome 7 centromeric probes, respectively. EGFR overexpression was observed in 26/35 (74.2%) cases and was correlated to the grade of the tumors and also to the history of the patients (p = 0.013, p = 0.036, respectively). Numerical alterations regarding gene and chromosome 7 were identified in 4/35 (11.4%) and 12/35 (43.2%) cases associated to the grade of the tumors (p = 0.019, p = 0.001, respectively) and to the survival rate of the patients (p = 0.037, p = 0.001, respectively). EGFR overall expression was also correlated to the gene copies (p = 0.020). EGFR gene numerical alterations -although rare- and also chromosome 7 aneuploidy maybe affect prognosis in HCC patients. To our knowledge this is the first chromogenic in situ hybridization analysis based on tissue microarrays in hepatocellular carcinoma.
authors.affiliation: Dept of Molecular Cytopathology, 417 NIMTS Hospital, Athens, Greece. tsiambasecyto@yahoo.gr
authors.forename: Evangelos
authors.initials: E
authors.lastname: Tsiambas
authors.forename: Loukas
authors.initials: L
authors.lastname: Manaios
authors.forename: Costas
authors.initials: C
authors.lastname: Papanikolopoulos
authors.forename: Dimitrios N
authors.initials: DN
authors.lastname: Rigopoulos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsounis
authors.forename: Andreas
authors.initials: A
authors.lastname: Karameris
authors.forename: Aspasia
authors.initials: A
authors.lastname: Soultati
authors.forename: Antigoni
authors.initials: A
authors.lastname: Koliopoulou
authors.forename: Christos
authors.initials: C
authors.lastname: Kravvaritis
authors.forename: Theodoros
authors.initials: T
authors.lastname: Sergentanis
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Spyridon
authors.initials: S
authors.lastname: Dourakis
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D066246:ErbB Receptors