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The Potential of BORIS Detected in the Leukocytes of Breast Cancer Patients as an Early Marker of Tumorigenesis

Authors' Affiliations: ¹ Department of Biological Sciences, University of Essex, Colchester, Essex, United Kingdom; ² Molecular Pathology Section, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland; ³ Grupo de Biología Molecular del Cáncer, Departamento de Biologia Molecular, Unidad de Biomedicina, Consejo Superior de Investigaciones Cientificas, Universidad de Cantabria; ⁴ Servicio de Hematología, Hospital Universitario Marqués de Valdecilla, Instituto de Formación e Investigación Marqués de Valdecilla, Santander, Spain; and ⁵ Helen Rollason Cancer Care Laboratory, Anglia Ruskin University, Chelmsford, Essex, United Kingdom

Requests for reprints: Elena Klenova, Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, United Kingdom. Phone: 44-0-1206-874868; Fax: 44-0-1206-872592; E-mail: klenovae{at}essex.ac.uk.

Purpose: Brother of the regulator of imprinted sites (BORIS) is a novel member of the cancer-testis antigen gene family. These genes are normally expressed only in spermatocytes but abnormally activated in different malignancies, including breast cancer. The aim of this study was to investigate the expression of BORIS in the leukocytes of breast cancer patients and the correlation between BORIS levels and clinical/pathologic variables.

Experimental Design: Leukocytes were obtained from whole blood of 87 breast cancer patients and 52 donors not diagnosed with cancer. BORIS protein was detected in leukocytes by immunohistochemical staining; the immunoreactivity score (IRS) of each sample was determined. Additionally, BORIS expression was assessed by Western blot analysis and real-time reverse transcription-PCR.

Results: We describe significantly high levels of BORIS (IRS = 4.25 ± 0.034) in a subpopulation of leukocytes, the neutrophil polymorphonuclear granulocytes, in 88.5% of breast cancer patients. Increased IRS for BORIS in these patients correlated with increased tumor size. In comparison, 19.2% samples from the control group were BORIS positive with only very low levels of BORIS (IRS = 0.25 ± 0.009).

Conclusion: We report here the novel finding of BORIS expression in polymorphonuclear granulocytes of breast cancer patients. This tumor-related occurrence is a phenomenon not observed in donors with injuries and immune and inflammatory diseases. Detection of BORIS in a high proportion of patients with various types of breast tumors indicates that BORIS can be a valuable early blood marker of breast cancer. We conclude that BORIS represents a new class of cancer biomarkers different from those currently used in medical practice.

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