Abstract

BackgroundMetadherin (MTDH) has been reported to be associated with cancer progression in various types of human cancers including breast cancer. Whether MTDH contributes to carcinogenesis of breast cancer is still unknown. In the present study, we investigated the expression of MTDH in normal, UDH (usual ductal hyperplasia), ADH (atypical ductal hyperplasia), DCIS (ductal carcinoma in situ) and invasive cancer to explore the possible role of MTDH for breast cancer carcinogenesis.MethodsImmunohistochemistry was employed on paraffin sections of surgical removed breast samples.ResultsThe immunohistochemical results showed almost no staining in normal tissue, moderate staining in ADH and UDH, intense MTDH stains in DCIS and cancer. Statistical analysis demonstrated significant different MTDH expression between proliferative and cancerous breast lesions (p < 0.001). MTDH was positively correlated with the histological differentiation of DCIS (p = 0.028). In breast cancer, statistical analysis revealed a significant correlation between MTDH expression with patients' age (p = 0.042), ER status (p = 0.018) and p53 status (p = 0.001). We also examined the effect of MTDH on cell proliferation in DCIS and cancer, and we found that MTDH overexpression was significantly correlated with high Ki67 index (p = 0.008 and p = 0.036, respectively).ConclusionsMTDH overexpression could be identified in proliferative breast lesions and may contribute to breast cancer progression.

Highlights

  • Metadherin (MTDH) has been reported to be associated with cancer progression in various types of human cancers including breast cancer

  • According to WHO Working Group on Pathology and Genetics of Tumors of the Breast, intraductal proliferative lesions have been divided into usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), flat epithelia atypia (FEA), and ductal carcinoma in situ (DCIS)

  • Expression of MTDH in UDH, ADH and DCIS A positive stain for MTDH was defined as brown stain observed in the cytoplasm (Figure 1)

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Summary

Introduction

Metadherin (MTDH) has been reported to be associated with cancer progression in various types of human cancers including breast cancer. We investigated the expression of MTDH in normal, UDH (usual ductal hyperplasia), ADH (atypical ductal hyperplasia), DCIS (ductal carcinoma in situ) and invasive cancer to explore the possible role of MTDH for breast cancer carcinogenesis. Metadherin (MTDH[2], known as astrocyte elevated gene-1(AEG-1)[3,4], and Lysine-rich CEACAM-1associated protein(Lyric)[5,6] was originally identified as an oncogene induced in primary human fetal astrocytes infected with human immunodeficiency virus type 1(HIV-1) or treated with HIV envelope glycoprotein(gp120) or tumor necrosis factor-α(TNF-α)[3,7]. Upregulation of MTDH increased lung metastasis of breast cancer cell, as well as migration and invasion of glioma cells All these studies suggest that MTDH plays important roles in the oncogenesis of these tumors. Besides the function of oncogenesis, MTDH was found to be a lipopolysaccharide(LPS)-responsive gene and involved in LPS-induced inflammatory response via NF-κB activation[17]

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