HER1-4 protein concentrations the same in normal and malignant bc tissue

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HER1-4 protein concentrations in normal breast tissue from breast cancer patients are expressed by the same profile as in the malignant tissue

Dorte Aa. Olsen1,
Birthe Østergaard2,
Susanne Bokmand3,
Peter A. Wamberg3,
Erik H. Jakobsen4,
Anders Jakobsen4,
Ivan Brandslund1,5,
1Department of Clinical Biochemistry, Vejle County Hospital, Vejle, Denmark
2Department of Pathology, Vejle County Hospital, Vejle, Denmark
3Breast Cancer Centre, Vejle County Hospital, Vejle, Denmark
4Department of Oncology, Vejle County Hospital, Vejle, Denmark
5The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
Corresponding author: Dorte Aa. Olsen, Department of Clinical Biochemistry, Vejle County Hospital, Kabbeltoft 25, 7100 Vejle, Denmark Phone: +45-79406633, Fax: +45-79406871,

Citation Information. Clinical Chemistry and Laboratory Medicine. Volume 0, Issue 0, Page -, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2009.214
Publication History: Received: 10/2/2009; accepted: 28/4/2009; published online: 24/06/2009
Abstract

Background: The epidermal growth factor receptor HER2 is overexpressed or amplified in 25%–30% of patients with breast cancer. The mechanism behind HER2 amplification is unknown, but may be a patho-physiological phenomenon caused by continuous stimulation and activation of the HER1-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation.
Methods: Tissue samples from malignant and adjacent normal breast tissue (autologous reference tissue) were collected from 118 women consecutively admitted for surgical treatment of breast cancer. In addition, 26 samples of normal breast tissue were collected from healthy women having breast reduction surgery. The tissue samples were homogenized and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method.
Results: HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8×10−6), while HER2 (p<10−7) and HER3 (p=3×10−5) were up regulated. Comparing autologous reference tissue with normal tissue showed down regulation of HER1 (p=0.122) and up regulation of HER2 (p=10−6), HER3 (p<10−7) and HER4 (p<10−7). Furthermore, we observed that correlations between the receptor combinations HER1-2, HER1-3 and HER1-4 were maintained from normal breast tissue to autologous reference breast tissue, but were lost in cancer tissue.
Conclusions: We suggest that these findings indicate that breast cancer is a systemic disease where the HER1-4 system in autologous reference tissue is continuously activated, thus favoring the subsequent development of cancer.
Clin Chem Lab Med 2009;47

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