title: HER2/CHR 17 tissue microarray chromogenic in situ hybridization analysis in colon adenocarcinoma: multiple gene signals vs protein expression.
abstract: OBJECTIVE
  HER2-dependent signalling pathway is deregulated in a subset of colon adenocarcinomas. Although HER2 protein expression patterns demonstrate a broad diversity in these tumors, the critical parameter for targeting the gene is the detection of gene amplification. Our aim was to investigate the correlation between HER2 protein levels and chromosome 17 (chr 17) copies.
  
  
  METHODS
  Sixty paraffin-embedded samples of primary colon adenocarcinomas were cored at 1 mm diameter and transferred to the microarray block. Immunohistochemistry (IHC) was performed using anti-HER2 monoclonal antibody. Chromogenic in situ hybridization (CISH) was performed using HER2 gene/chromosome 17 centromeric probes.
  
  
  RESULTS
  HER2 protein overexpression (score: 2+/3+) was observed in 20/60 (33.3%) samples. CISH analysis detected 11/60 (18.33%) amplified cases, whereas chromosome 17 aneuploidy (polysomy) was identified in 13/60 (21.66%) cases. Significant associations were detected correlating HER2 expression with grade of the tumors (p=0.03), Chr 17 with stage (p=0.01), gene copies with protein expression (p=0.008), and also Chr 17 centromere signals with overall gene signals (p=0.001).
  
  
  CONCLUSIONS
  Multiple HER2 gene copies lead to different protein expression patterns (score 1+ to 3+) but pure gene amplification is only a subset of them. Identification of chromosome polysomy is a critical parameter in detecting original gene amplification in conventional one-color CISH methods.
authors.affiliation: Department of Surgery, 424 General Army Hospital, Thessaloniki, Greece.
authors.forename: Panagiotis P
authors.initials: PP
authors.lastname: Fotiades
authors.forename: Evangelos
authors.initials: E
authors.lastname: Tsiambas
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Lazaris
authors.forename: Angeliki A
authors.initials: AA
authors.lastname: Saetta
authors.forename: Andreas
authors.initials: A
authors.lastname: Karameris
authors.forename: George
authors.initials: G
authors.lastname: Vilaras
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D016612:Paraffin Embedding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human