This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stoecklein, N. H. Articles by Hosch, S. B. Search for Related Content PubMed PubMed Citation Articles by Stoecklein, N. H. Articles by Hosch, S. B. Social Bookmarking                            What's this?

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. J. Liang, H. Wang, A. Rashid, T.-H. Tan, R. F. Hwang, S. R. Hamilton, J. L. Abbruzzese, D. B. Evans, and H. Wang Expression of MAP4K4 Is Associated with Worse Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma Clin. Cancer Res., November 1, 2008; 14(21): 7043 - 7049. [Abstract] [Full Text] [PDF]

				K. Kimura, T. Sawada, M. Komatsu, M. Inoue, K. Muguruma, T. Nishihara, Y. Yamashita, N. Yamada, M. Ohira, and K. Hirakawa Antitumor Effect of Trastuzumab for Pancreatic Cancer with High HER-2 Expression and Enhancement of Effect by Combined Therapy with Gemcitabine. Clin. Cancer Res., August 15, 2006; 12(16): 4925 - 4932. [Abstract] [Full Text] [PDF]