Preserved Axin expression is associated with an aggressive phenotype in invasive breast carcinomas

APMIS. 2013 Sep;121(9):797-805. doi: 10.1111/apm.12037. Epub 2012 Dec 20.

Abstract

Reduced Axin expression has been associated with an aggressive behavior in lung and esophageal squamous cell carcinomas. Its role in breast cancer has not been defined. The aim of our study was to investigate the expression pattern of Axin protein in invasive breast carcinomas, in relation to the behavior and prognosis of the disease. Immunohistochemistry was performed for the detection of Axin expression in 232 breast cancer tissues. Univariate and multivariate statistical analyses were used to assess the relation of Axin expression with classic clinicopathological parameters, patients' survival and various biologic markers Human Epidermal Factor-2 (HER-2), Ki-67, topoIIα, glycogen synthase kinase-3β (GSK-3β)]. Preserved cytoplasmic Axin expression was positively correlated to lymph node invasion, HER-2 and GSK-3β and inversely to Ki-67 and topoIIα. Nuclear Axin was positively associated with tumor size. Stromal Axin showed a parallel association with lymph node status and HER-2. In the subgroup of lobular breast carcinomas, preserved Axin was found to exert an unfavorable impact on patients' overall survival. Our findings indicate, for the first time, that in invasive breast cancer preserved Axin expression is associated with a more aggressive phenotype and that in the discrete subtype of lobular breast carcinomas Axin negatively influences patients' overall survival.

Keywords: Axin; aggressive phenotype; breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Axin Protein / genetics*
  • Axin Protein / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / diagnosis
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Lobular / diagnosis
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Invasiveness
  • Phenotype
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Survival Analysis

Substances

  • Antigens, Neoplasm
  • Axin Protein
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • DNA Topoisomerases, Type II