title: Copy number of chromosome 17 but not HER2 amplification predicts clinical outcome of patients with pancreatic ductal adenocarcinoma.
abstract: OBJECTIVE
  To determine the frequency and the potential clinical use of HER2 (17q21) gene amplification and chromosome 17 aneuploidy in pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Serial tissue sections of 50 resected PDACs were analyzed with chromogenic in situ hybridization using locus-specific HER2 probes and centromeric probes for chromosome 17. Centromeric probes for chromosome 7 and 8 were hybridized to confirm ploidy levels. Expression of HER2 protein was assessed by immunohistochemistry. Correlations of experimental findings with clinical and follow-up data were tested.
  
  
  RESULTS
  The HER2 gene locus was frequently (24%) amplified in PDAC and the rate of overexpression (2+ and 3+) was 10%, but no prognostic significance was found. Copy number analysis of chromosomes 7, 8, and 17 revealed disomic (40%), trisomic (36%), and hypertetrasomic (24%) tumors. Compared with patients with disomic tumors, patients with hypertetrasomic tumors exhibited a significantly decreased relapse-free and overall survival (5.0 v 13.0 months, P = .0144 and 7.0 v 20.0 months, P = .0099, respectively). Multivariate analysis confirmed the independent prognostic significance of hypertetrasomy.
  
  
  CONCLUSIONS
  Tumor ploidy levels correlate with prognosis of PDAC patients, indicating characteristic biologic properties of PDAC with high chromosomal instability. In contrast, no prognostic influence on patient outcome was found for the amplification of the HER2 oncogene or p185(HER2) overexpression. Therefore, evaluation of ploidy levels offers new opportunities for patient stratification in clinical trials and enables novel approaches to study the well-known aggressiveness of PDAC.
authors.affiliation: Chirurgische Klinik, and Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. Nikolas.Stoecklein@uni-duesseldorf.de
authors.forename: Nikolas H
authors.initials: NH
authors.lastname: Stoecklein
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Luebke
authors.forename: Andreas
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: Wolfram T
authors.initials: WT
authors.lastname: Knoefel
authors.forename: Winfried
authors.initials: W
authors.lastname: Schraut
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Verde
authors.forename: Franziska
authors.initials: F
authors.lastname: Stern
authors.forename: Peter
authors.initials: P
authors.lastname: Scheunemann
authors.forename: Matthias
authors.initials: M
authors.lastname: Peiper
authors.forename: Claus F
authors.initials: CF
authors.lastname: Eisenberger
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Klein
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Hosch
mesh_terms: D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002886:Chromosomes, Human, Pair 17; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015999:Multivariate Analysis; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D012494:Sampling Studies; D015996:Survival Rate; D046509:Tissue Culture Techniques
chemical_list: D014408:Biomarkers, Tumor