Increased expression of brother of the regulator of imprinted sites in peripheral blood neutrophils is associated with both benign and malignant breast lesions

Cytometry B Clin Cytom. 2017 Sep;92(5):355-360. doi: 10.1002/cyto.b.21378. Epub 2016 May 24.

Abstract

Background: BORIS, a paralog of the multifunctional CCCTC-binding factor (CTCF) gene is restricted to testis and normally not present in females. It is aberrantly activated in various human cancers including cancer breast. Using immunohistochemistry, western blot and/or RT-PCR, significantly higher levels of BORIS expression were reported in the neutrophils of cancer breast patients. We hypothesized that Flow Cytometry might be a better technique for objective quantitative evaluation of BORIS in neutrophils and we wanted to investigate if BORIS would discriminate between benign and malignant breast lesions.

Methods: The study included 85 females; 52 breast cancer, 13 benign breast lesions and 20 age-matched healthy controls. BORIS expression in the neutrophils was detected by Flow Cytometry.

Results: High level of BORIS was detected in all malignant (64.4 ± 16.6%) and benign cases (67 ± 12.3), mean florescent intensity ratio (MFIR) of 7.2 ± 4.1 and 7 ± 3.5, median 5.8 and 6.6%; and staining index (SI) 8.3 ± 3.9 and 8.2 ± 3.4, median 7.6 and 7.9 respectively vs.13.4 ± 11.5% MFI 1.8 ± 0.7, median1.6 and SI 2.6 ± 0.69, median 2.5 for the control. BORIS level was comparable in the malignant and benign group (P = 0.934) and significantly higher than control (P = 0.0001). There was no correlation between neutrophil BORIS expression and ER/PR status, HER-2/neu expression or tumor stage or size.

Conclusions: Increased BORIS expression in peripheral blood neutrophils is associated with both benign and malignant breast lesions; apparently, increased proliferation of breast tissue is the determining factor. This excludes BORIS as a tumor marker but it does not jeopardize its value as a potential therapeutic target. © 2016 International Clinical Cytometry Society.

Keywords: BORIS; breast cancer; flow cytometry; indirect cytoplasmic staining; neutrophils.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Flow Cytometry / methods
  • Frizzled Receptors / immunology
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Neoplasms / metabolism
  • Neutrophils / cytology*
  • RNA, Messenger / metabolism

Substances

  • Biomarkers, Tumor
  • FZD9 protein, human
  • Frizzled Receptors
  • RNA, Messenger