Copy number of chromosome 17 but not HER2 amplification predicts clinical outcome of patients with pancreatic ductal adenocarcinoma.
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.
Stoecklein
Nikolas H
NH
Chirurgische Klinik, and Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany. Nikolas.Stoecklein@uni-duesseldorf.de
Luebke
Andreas M
AM
Erbersdobler
Andreas
A
Knoefel
Wolfram T
WT
Schraut
Winfried
W
Verde
Pablo E
PE
Stern
Franziska
F
Scheunemann
Peter
P
Peiper
Matthias
M
Eisenberger
Claus F
CF
Izbicki
Jakob R
JR
Klein
Christoph A
CA
Hosch
Stefan B
SB
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
D014408:Biomarkers, Tumor