title: EGFR alterations in pancreatic ductal adenocarcinoma: a chromogenic in situ hybridization analysis based on tissue microarrays.
abstract: OBJECTIVE
  To evaluate epidermal growth factor receptor (EGFR) gene status in pancreatic ductal adenocarcinoma correlating the results to protein expression and clinicopathological features
  
  
  METHODS
  Using tissue microarray technology (TMArrayer 100), fifty (n = 50) paraffin-embedded tissue samples of histologically-confirmed primary tumors were cored twice at a diameter of 1 mm and re-embedded into the final recipient block. Immunohistochemistry was performed by the use of anti-EGFR monoclonal antibody (31G7). Also, a chromogenic in situ hybridization protocol was applied based on the use of EGFR gene and chromosome 7 centromeric probes, respectively.
  
  
  RESULTS
  EGFR protein overexpression was observed in 29/50 (58%) cases and correlated to stage (p = 0.001) but not to grade (p = 0.206). EGFR gene analysis identified numerical alterations in 6/50 (12%), including 2 cases characterized by low-level gene amplification and 4 by absence of one allele. Gene status was associated to tumor grade (p = 0.023) and stage (p = 0.02). Chromosome 7 analysis detected aneuploidy in 14 (28%) cases.
  
  
  CONCLUSIONS
  A subset of pancreatic ductal adenocarcinomas (PDACs) is characterized by EGFR gene numerical alterations including sporadic cases of amplification or absence of one allele (maybe due to gene deletion or intragenic point mutation and allelic silence). Those alternative mechanisms maybe influence the efficacy of novel targeted therapeutic strategies based on monoclonal antibodies or intracellular tyrosine-kinase inhibitors in PDACs.
authors.affiliation: Department of Molecular Pathology, Tissue Microarrays and Image Analysis Lab, 417 VA (NIMTS) Hospital Athens, Greece. tsiambasecyto@yahoo.gr
authors.forename: Evangelos
authors.initials: E
authors.lastname: Tsiambas
authors.forename: Andreas
authors.initials: A
authors.lastname: Karameris
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Lazaris
authors.forename: Maroulio
authors.initials: M
authors.lastname: Talieri
authors.forename: John K
authors.initials: JK
authors.lastname: Triantafillidis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Cheracakis
authors.forename: Loukas
authors.initials: L
authors.lastname: Manaios
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Gerontopoulos
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Nikolaos J
authors.initials: NJ
authors.lastname: Lygidakis
mesh_terms: D000368:Aged; D000782:Aneuploidy; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002863:Chromogenic Compounds; D002897:Chromosomes, Human, Pair 7; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D002863:Chromogenic Compounds; D066246:ErbB Receptors