PURPOSE: The HER2 oncogene is involved in the biology of many different tumor types and serves as a prognostic marker and a therapeutic target in breast cancer. In contrast to breast cancer, studies on Her2 overexpression and gene amplification in prostate cancer have yielded different results. The purpose of this study was to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in prostate cancer. EXPERIMENTAL DESIGN: A tissue microarray containing >2,000 prostate cancers with follow-up data was used. Tissue microarray sections were analyzed on protein and DNA level using two different antibodies (HercepTest, DAKO; Novocastra NCL-CB11) and fluorescence in situ hybridization. RESULTS: Immunohistochemical analyses showed highly similar results for both antibodies. Detectable Her2 immunostaining was observed in 17.2% for the HercepTest and in 22.5% for the Novocastra antibody with the vast majority of cases showing 1+ or 2+ staining. For both antibodies (HercepTest/Novocastra), significant associations were found between positive staining and high Gleason grade (P < 0.0001, both), advanced pT stage (P < 0.0001/P = 0.0015), rapid tumor cell proliferation (P = 0.0004/P = 0.0071), and tumor recurrence (P < 0.0001, both). HER2 amplification was only found in 1 of 2,525 analyzable cases (0.04%). CONCLUSIONS: Low-level Her2 overexpression occurs at relevant frequency in prostate cancer and in the absence of gene amplification. Increased Her2 expression may potentially lead to an aggressive behavior of tumor cells through the stimulation of tumor cell proliferation because Her2 staining was shown to be significantly associated with Ki67 labeling index. These data argue for reconsidering anti-Her2 therapy, possibly with modified approaches.
PURPOSE: The HER2 oncogene is involved in the biology of many different tumor types and serves as a prognostic marker and a therapeutic target in breast cancer. In contrast to breast cancer, studies on Her2 overexpression and gene amplification in prostate cancer have yielded different results. The purpose of this study was to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in prostate cancer. EXPERIMENTAL DESIGN: A tissue microarray containing >2,000 prostate cancers with follow-up data was used. Tissue microarray sections were analyzed on protein and DNA level using two different antibodies (HercepTest, DAKO; Novocastra NCL-CB11) and fluorescence in situ hybridization. RESULTS: Immunohistochemical analyses showed highly similar results for both antibodies. Detectable Her2 immunostaining was observed in 17.2% for the HercepTest and in 22.5% for the Novocastra antibody with the vast majority of cases showing 1+ or 2+ staining. For both antibodies (HercepTest/Novocastra), significant associations were found between positive staining and high Gleason grade (P < 0.0001, both), advanced pT stage (P < 0.0001/P = 0.0015), rapid tumor cell proliferation (P = 0.0004/P = 0.0071), and tumor recurrence (P < 0.0001, both). HER2 amplification was only found in 1 of 2,525 analyzable cases (0.04%). CONCLUSIONS: Low-level Her2 overexpression occurs at relevant frequency in prostate cancer and in the absence of gene amplification. Increased Her2 expression may potentially lead to an aggressive behavior of tumor cells through the stimulation of tumor cell proliferation because Her2 staining was shown to be significantly associated with Ki67 labeling index. These data argue for reconsidering anti-Her2 therapy, possibly with modified approaches.
Authors: Michael J Cima; Heejin Lee; Karen Daniel; Laura M Tanenbaum; Aikaterini Mantzavinou; Kevin C Spencer; Qunya Ong; Jay C Sy; John Santini; Carl M Schoellhammer; Daniel Blankschtein; Robert S Langer Journal: J Control Release Date: 2014-05-04 Impact factor: 9.776
Authors: Kathleen C Day; Guadalupe Lorenzatti Hiles; Molly Kozminsky; Scott J Dawsey; Alyssa Paul; Luke J Broses; Rajal Shah; Lakshmi P Kunja; Christopher Hall; Nallasivam Palanisamy; Stephanie Daignault-Newton; Layla El-Sawy; Steven James Wilson; Andrew Chou; Kathleen Woods Ignatoski; Evan Keller; Dafydd Thomas; Sunitha Nagrath; Todd Morgan; Mark L Day Journal: Cancer Res Date: 2016-10-28 Impact factor: 12.701
Authors: Christoph Burdelski; Tatsiana Dieckmann; Asmus Heumann; Claudia Hube-Magg; Martina Kluth; Burkhard Beyer; Thomas Steuber; Raisa Pompe; Markus Graefen; Ronald Simon; Sarah Minner; Maria Christina Tsourlakis; Christina Koop; Jakob Izbicki; Guido Sauter; Till Krech; Thorsten Schlomm; Waldemar Wilczak; Patrick Lebok Journal: Tumour Biol Date: 2016-07-21