Originally published as JCO Early Release 10.1200/JCO.2005.04.8397 on August 8 2006

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ErbB-3 Predicts Survival in Ovarian Cancer

Berno Tanner, Dirk Hasenclever, Katja Stern, Wiebke Schormann, Martin Bezler, Matthias Hermes, Marc Brulport, Alexander Bauer, Ilka B. Schiffer, Susanne Gebhard, Markus Schmidt, Eric Steiner, Jalid Sehouli, Jeanett Edelmann, Jürgen Läuter, Rüdiger Lessig, K. Krishnamurthi, Axel Ullrich, Jan Georg Hengstler

From the Department of Gynecology and Obstetrics, University of Mainz, Mainz; Institute of Medical Informatics, Statistics and Epidemiology, Center for Toxicology, Institute of Legal Medicine and Rudolf-Boehm-Institute of Pharmacology and Toxicology, Interdisciplinary Centre for Bioinformatics (IZBI), University of Leipzig, Leipzig; Department of Molecular Biology, Max-Planck-Institute for Biochemistry, Martinsried; Department of Obstetrics and Gynecology, Charite, Berlin; Institute für Biometry and Medical Informatics, Otto-von-Guericke-University; Institute for Biometry and Medical Informatics, University of Magdeburg, Magdeburg, Germany; Environmental Biotechnology Division, National Environmental Engineering Research Institute, Nehru Marg, Nagpur, India

Address reprint requests to Jan G. Hengstler, MD, Center for Toxicology, (Institute of Legal Medicine and Rudolf-Boehm Institute of Pharmacology and Toxicology), Hartelstr. 16-18, University of Leipzig, 04107 Leipzig, Germany; e-mail: jan.hengstler{at}medizin.uni-leipzig.de

Background HER3 (erbB-3) is a member of the epidermal growth factor receptor (EGFR) family. After dimerization with other members of the EGFR family several signal transduction cascades can be activated, including phosphoinosite 3'-kinase (PI3-K)/Akt and extracellular signal-regulated kinase (ERK1/2). Here, we studied a possible association between HER3 expression and prognosis in patients with ovarian cancer.

Methods Tumor tissue of 116 consecutive patients diagnosed with primary epithelial ovarian cancer between 1986 and 1995 was analyzed immunohistochemically for HER3 expression. A possible influence of HER3 expression on survival was studied by multivariate Cox regression adjusting for established clinical prognostic factors.

Results A positive HER3 expression was observed in 53.4% of the patients. HER3 expression was associated with decreased survival in proportional hazard modeling, including the International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade and type, residual disease, and age. After likelihood ratio forward as well as backward selection, only HER3 expression (hazard ratio, 1.71; 95% CI, 1.10 to 2.67; P = .018), FIGO stage (hazard ratio, 4.78; 95% CI, 1.89 to 12.08; P = .001), residual tumor (hazard ratio, 2.69; 95% CI, 1.40 to 5.17; P = .003), and age (hazard ratio, 2.06; 95% CI, 1.17 to 3.65; P = .013) were found to be significant. Kaplan-Meier plots demonstrated a clear influence of HER3 expression on survival time. Median survival time was 3.31 years (95% CI, 1.93 to 4.68) for patients with low HER3 expression, compared with only 1.80 years (95% CI, 0.83 to 2.78) for patients with HER3 overexpression (log-rank test P = .0034).

Conclusion HER3 may represent a new prognostic factor in primary epithelial ovarian cancer. Pending validation, exploration of therapeutic strategies to block HER3 could be warranted.

published online ahead of print at www.jco.org on August 7, 2006.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

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

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