Immunohistochemical expression of erythropoietin and erythropoietin receptor in breast carcinoma

Authors

  • Geza Acs M.D., Ph.D.,

    Corresponding author
    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
    • Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, 6 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA 19104
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    • Fax: (215) 349-5910

  • Paul J. Zhang M.D.,

    1. Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
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  • Timothy R. Rebbeck Ph.D.,

    1. Center for Clinical Epidemiology and Biostatistics and Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Peter Acs M.D., Ph.D.,

    1. Department of Medicine, Huron Hospital, Cleveland Clinic Health System, Cleveland, Ohio
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  • Ajay Verma M.D., Ph.D.

    1. Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland
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Abstract

BACKGROUND

Erythropoietin (Epo), induced by hypoxia, controls the survival, proliferation, and differentiation of Epo receptor (EpoR)-bearing erythroid progenitors and plays a role in the protection of neurons from hypoxic damage. Hypoxia in malignant disease is associated with invasion, metastasis, resistance to therapy, and selection for cells with diminished apoptotic potential. The authors recently demonstrated the basal and hypoxia-stimulated expression of Epo and EpoR in human breast carcinoma cell lines and in breast carcinomas, suggesting a role for autocrine Epo signaling in the hypoxic adaptations of mammary neoplasms.

METHODS

The authors characterized the expression of Epo and EpoR by immunohistochemistry in 184 invasive mammary carcinomas and 158 in situ mammary carcinomas and benign mammary epithelium. They analyzed the correlation of Epo and EpoR immunostaining with clinicopathologic tumor features and the patients' smoking history.

RESULTS

Benign mammary epithelial cells showed weak-to-moderate expression of Epo and EpoR. EpoR immunostaining was increased in carcinomas compared with benign epithelium both in nonsmokers and smokers, and Epo immunostaining was increased in carcinomas compared with benign epithelium in nonsmokers but not in smokers. Prominent Epo staining was seen in tumor cells adjacent to necrotic areas and at the infiltrating edge of tumors. EpoR staining, but not Epo staining, was significantly greater in tumors that showed high histologic grade, tumor necrosis, lymphovascular invasion, lymph node metastases, and loss of hormone receptor expression.

CONCLUSIONS

The current findings suggest that increased EpoR expression may play an important role in breast carcinogenesis. The induction of autocrine or paracrine Epo signaling may represent a novel mechanism by which hypoxia can promote breast carcinoma. Cancer 2002;95:969–81. © 2002 American Cancer Society.

DOI 10.1002/cncr.10787

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