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Copy Number of Chromosome 17 but Not HER2 Amplification Predicts Clinical Outcome of Patients With Pancreatic Ductal Adenocarcinoma

From the Chirurgische Klinik, and Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg; Institut für Immunologie, Ludwig-Maximilians-Universität München, München; and Koordinierungszentrum für klinische Studien, Universitätsklinikum Düsseldorf, Düsseldorf, Germany

Address reprint requests to Nikolas H. Stoecklein, MD, Klinik für Allgemein-und Viszeralchirugie, Universitätsklinikum Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany; e-mail: Nikolas.Stoecklein{at}uni-duesseldorf.de

PURPOSE: To determine the frequency and the potential clinical use of HER2 (17q21) gene amplification and chromosome 17 aneuploidy in pancreatic ductal adenocarcinoma (PDAC).

MATERIALS AND 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.

CONCLUSION: 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.

Supported in part by a grant from the Hamburger Krebsgesellschaft, a grant from the Deutsche Forschungsgemeinschaft STO 464/1-1, and by a grant from the Werner Otto Stiftung.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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