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LCN2 Promoter Methylation Status as Novel Predictive Marker for Microvessel Density and Aggressive Tumor Phenotype in Breast Cancer Patients

  • Meka, Phanni bhushann (Department of Genetics, Osmania University) ;
  • Jarjapu, Sarika (Department of Genetics, Osmania University) ;
  • Nanchari, Santhoshi Rani (Department of Genetics, Osmania University) ;
  • Vishwakarma, Sandeep Kumar (Deccan College of Medical Sciences) ;
  • Edathara, Prajitha Mohandas (Department of Genetics, Osmania University) ;
  • Gorre, Manjula (Department of Genetics, Osmania University) ;
  • Cingeetham, Anuradha (Department of Genetics, Osmania University) ;
  • Vuree, Sugunakar (Department of Genetics, Osmania University) ;
  • Annamaneni, Sandhya (Department of Genetics, Osmania University) ;
  • Dunna, Nageswara Rao (School of Chemical & Biotechnology, Sastra University) ;
  • Mukta, Srinivasulu (MNJ Institute of Oncology & Regional Cancer Centre) ;
  • Triveni, B (MNJ Institute of Oncology & Regional Cancer Centre) ;
  • Satti, Vishnupriya (Department of Genetics, Osmania University)
  • Published : 2015.07.13

Abstract

LCN2 (Lipocalin 2) is a 25 KD secreted acute phase protein, reported to be a novel regulator of angiogenesis in breast cancer. Up regulation of LCN2 had been observed in multiple cancers including breast cancer, pancreatic cancer and ovarian cancer. However, the role of LCN2 promoter methylation in the formation of microvessels is poorly understood. The aim of this study was to analyze the association of LCN 2 promoter methylation with microvessel formation and tumor cell proliferation in breast cancer patients. The LCN2 promoter methylation status was studied in 64 breast cancer tumors by methylation specific PCR (MSP). Evaluation of microvessel density (MVD) and Ki67 cell proliferation index was achieved by immunohistochemical staining using CD34 and MIB-1 antibodies, respectively. LCN2 promoter unmethylation status was observed in 43 (67.2%) of breast cancer patients whereas LCN2 methylation status was seen in 21 (32.8%). Further, LCN2 promoter unmethylation status was associated with aggressive tumor phenotype and elevated mean MVD in breast cancer patients.

Keywords

Lipocalin 2;DNA methylation;microvessel density;cell proliferation;breast cancer

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