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Hum Pathol. 2010 Nov;41(11):1577-85. doi: 10.1016/j.humpath.2010.02.018. Epub 2010 Jul 24.

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

Author information

1
Institute for Pathology, Hubertus Wald Tumorzentrum-University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. a.marx@uke.de

Abstract

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.

PMID:
20656317
DOI:
10.1016/j.humpath.2010.02.018
[Indexed for MEDLINE]

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