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

Abstract

LCN2 (Lipocalin 2) is a 25 KD secreted acute phase protein, reported to be a novel regulator of angiogenesis inbreast cancer. Up regulation of LCN2 had been observed in multiple cancers including breast cancer, pancreaticcancer and ovarian cancer. However, the role of LCN2 promoter methylation in the formation of microvesselsis poorly understood. The aim of this study was to analyze the association of LCN 2 promoter methylation withmicrovessel formation and tumor cell proliferation in breast cancer patients. The LCN2 promoter methylationstatus was studied in 64 breast cancer tumors by methylation specific PCR (MSP). Evaluation of microvesseldensity (MVD) and Ki67 cell proliferation index was achieved by immunohistochemical staining using CD34and MIB-1 antibodies, respectively. LCN2 promoter unmethylation status was observed in 43 (67.2%) of breastcancer patients whereas LCN2 methylation status was seen in 21 (32.8%). Further, LCN2 promoter unmethylationstatus was associated with aggressive tumor phenotype and elevated mean MVD in breast cancer patients.