Clinicopathological significance of ARID1B in breast invasive ductal carcinoma

Histopathology. 2015 Nov;67(5):709-18. doi: 10.1111/his.12701. Epub 2015 May 17.

Abstract

Aims: Identification of prognostic and predictive biomarkers for breast cancer is essential to better stratify patients for treatment and evaluate patient outcome. AT-rich interactive domain-containing protein 1B (ARID1B) is implicated in cell proliferation, but its role in tumorigenesis remains unclear.

Methods and results: Immunohistochemical analysis of ARID1B expression using breast cancer tissue microarrays containing 156 breast invasive ductal carcinoma patient samples and subsequent statistical data analysis based on ARID1B immunoreactivity score were performed to examine the correlation between clinicopathological parameters in breast cancer and ARID1B expression. In-vitro assays were also performed to study the role of ARID1B in cell cycle progression. Univariate analysis revealed that high ARID1B expression is correlated closely with histological grade (P = 0.045) and size (P = 0.043) of invasive breast cancer. These findings were confirmed by multivariate analysis. Notably, increased ARID1B expression was frequently detected in the aggressive triple-negative breast cancer subtypes (P = 0.039) and associated with decreased 5-year disease-free survival rate. Lastly, MDA-MB-231 cells with reduced ARID1B activity displayed a delay in G1 to S phase cell cycle transition and consequently showed a decrease in cell proliferation compared with controls (P < 0.001).

Conclusions: ARID1B potentially serves as a valuable prognostic and predictive biomarker as well as a therapeutic target in breast cancer.

Keywords: ARID1B; breast cancer; immunohistochemistry; proliferation; tissue microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology*
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Tissue Array Analysis
  • Transcription Factors / analysis
  • Transcription Factors / biosynthesis*
  • Transfection

Substances

  • ARID1B protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • RNA, Small Interfering
  • Transcription Factors