The Potential of BORIS Detected in the Leukocytes of Breast Cancer Patients as an EarlyMarker ofTumorigenesis

Purpose: Brother of the regulator of imprinted sites (BORIS) is a novel member of the cancertestis 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 BORISin 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 byWestern blot analysis and real-time reverse transcription-PCR.
Results:We describe significantly high levels of BORIS (IRS = 4.25F 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 fromthe control groupwere BORIS positivewith only very lowlevels ofBORIS (IRS = 0.25 F 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 inmedical practice.