Abstract

The nuclear factor κB (NF-κB) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-κB /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. In this hospital based study 57 breast cancer patients attending a Breast Clinic of a reputed institute of Eastern India were assessed for p65 protein expression in breast tumor tissue samples by Western blotting. ER, PR and HER-2/neu expression was determined by immunohistochemistry. NF-κB/p65 was significantly associated with advanced stage, large tumor size (≥5 cm), high grade, negative ER, negative PR, and positive HER-2/neu. High NF-κB/p65 expression was more frequent in patients with a high NPI (NPI≥5.4, 84.6%) compared with low NPI (<5.4, 44.4%) and this association was statistically significant (p=0.002). NF-κB/p65 overexpression was associated with advanced stage, large tumor size, high grade, and high NPI which are poor prognostic factors linked to enhanced aggressiveness of the disease. NF-κB/p65 expression implies aggressive biological behavior of breast cancer and this study validates significant association of NF-κB /p65 overexpression with negative estrogen and progesterone receptor status and overexpression of HER-2/neu oncoprotein. In our good clinical practice, patients with NF-κB positive tumors need to be treated aggressively.

Highlights

  • The nuclear factor κB (NF-κB) is a super family of transcription factors which plays important roles in development and progression of cancer

  • This study aims to validate the role of activation of NF-κB/p65 as a prognostic marker in patients with breast cancer in Indian subcontinent

  • Patient selection The patients were divided into two groups, first group (Group-A) comprised of 57 female patients with invasive ductal carcinoma (IDC) previous untreated by chemotherapy, radiotherapy, hormone therapy or a combination of any of the modalities who presented to the Comprehensive Breast Clinic Service and Breast Cancer Research Unit, IPGME and R/Seth Sukhlal Karnani Memorial Hospital (SSKM) Hospital, Kolkata, West Bengal, India between 2008 and 2011 were included in this research work. 23 female patients who were histological and clinically fibro adenoma or benign breast disease treated as control group (Group-B)

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Summary

Introduction

The nuclear factor κB (NF-κB) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-κB /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. In eastern India, BC is the most frequently reported cancer (22.7%) in females and the age-specific incidence rate is 25.1 per 100,000 populations (Sen et al, 2002).Breast cancer survival depends on various molecular factors. It becomes important to know about the nature of the disease, so as to ensure optimum adjuvant therapy and predict the course of outcome (Sarkar et al, 2009). NF-κB regulates over 500 genes involved in cellular transformation, survival, proliferation, invasion, Asian Pacific Journal of Cancer Prevention, Vol 13, 2012 5511

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