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Expression of erbB/HER receptors, heregulin and p38 in primary breast cancer using quantitative immunohistochemistry

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Pathology Oncology Research

Abstract

The purpose of this study was to investigate the frequency of expression of the erbB/HER family of growth factor receptors, their ligand heregulin, and the two different signaling pathways p38 and mitogen-activated protein kinase (MAPK), as well as the status of HER-2 phosphorylation in tumor specimens from patients with primary breast cancer. The level of expression of these proteins was measured by quantitative immunohistochemistry combined with microscope-based image analysis in paraffin-embedded breast cancer tissue from 35 patients. The frequency of expression was: EGFR (51%), HER-2 (54%), P-HER-2 (48%), HER-3 (48%), HER-4 (57%), heregulin (48%), p38 (17%), MAPK (48%). There was evidence of associations among the coexpression of heregulin, EGFR, HER-2, and HER-3. Also, there was evidence of a positive association between P-MAPK and HER-4. HER-3 was expressed at high levels in patients younger than 50 years of age. There was a trend for expression of higher levels of HER-4 in tumors larger than 2 cm. The expression of EGFR, HER-2, heregulin, p38 and MAPK was independent of age, tumor size, number of lymph nodes involved or hormone receptor status. The HER family of growth factor receptors appear to be regulated independently in invasive breast cancer. Assessing the expression of multiple tumor markers by quantitative immunohistochemistry is feasible. Further research is needed to determine the prognostic and predictive roles of the various associations between HER receptors, their ligands and signal transduction molecules in patients with early-stage breast cancer.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

    Francisco J. Esteva, Gabriel N. Hortobagyi, Lajos Pusztai, Aman U. Buzdar & Sarah S. Bacus

  2. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

    Aysegul A. Sahin

  3. Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

    Terry L. Smith & Shang -Ying Liang

  4. Quantitative Diagnostics Laboratory, Elmhurst, Illinois, USA

    Dot Mon Chin & Sarah S. Bacus

Authors
  1. Francisco J. Esteva
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  2. Gabriel N. Hortobagyi
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  3. Aysegul A. Sahin
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  4. Terry L. Smith
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  7. Lajos Pusztai
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  8. Aman U. Buzdar
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  9. Sarah S. Bacus
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Esteva, F.J., Hortobagyi, G.N., Sahin, A.A. et al. Expression of erbB/HER receptors, heregulin and p38 in primary breast cancer using quantitative immunohistochemistry. Pathol. Oncol. Res. 7, 171–177 (2001). https://doi.org/10.1007/BF03032345

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  • DOI: https://doi.org/10.1007/BF03032345

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