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Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers

Summary HER-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti–HER-2 therapy is currently investigated in several other HER-2 amplified cancers. For example, trastuzumab was recently shown to be effective in HER-2 positive gastric can...

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Published in:Human pathology 2010-11, Vol.41 (11), p.1577-1585
Main Authors: Marx, Andreas H., MD, Burandt, Eike C., MD, Choschzick, Matthias, MD, Simon, Ronald, PhD, Yekebas, Emre, MD, Kaifi, Jussuf T., MD, Mirlacher, Martina, MD, Atanackovic, Djordje, MD, Bokemeyer, Carsten, MD, Fiedler, Walter, MD, Terracciano, Luigi, MD, Sauter, Guido, MD, Izbicki, Jakob R., MD
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Language:English
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Summary:Summary HER-2 is the molecular target for antibody-based treatment of breast cancer (trastuzumab). The potential benefit of anti–HER-2 therapy is currently investigated in several other HER-2 amplified cancers. For example, trastuzumab was recently shown to be effective in HER-2 positive gastric cancer. To address the potential applicability of anti–HER-2 therapy in colorectal cancer, tissue microarray sections and colorectal resection specimens of 1851 colorectal cancers were analyzed for HER-2 overexpression and amplification using FDA approved reagents for immunohistochemistry and fluorescence in situ hybridization. HER-2 amplification was seen in 2.5% and HER-2 overexpression in 2.7% of 1439 interpretable colorectal cancers. Amplification was often high level with HER-2 copies ranging from 4 to 60 per tumor cell and was strongly related to protein overexpression. HER-2 amplification and overexpression were unrelated to histological tumor type, tumor localization, grading, pT, pN, pM or survival. As heterogeneity of drug target expression could represent a major drawback for targeted cancer therapy we next studied HER-2 heterogeneity in selected cases. Extensive evaluation of all available large sections from patients with HER-2 positive colorectal cancer revealed heterogenous findings in 3 of 4 cases. In summary, high-level HER-2 amplification occurs in a small fraction of colorectal cancers. Heterogeneity of amplification may limit the utility of anti- HER-2 therapy in some of these tumors and therefore, adequate clinical trials are needed to further evaluate this approach.
ISSN:0046-8177
1532-8392
DOI:10.1016/j.humpath.2010.02.018