J Breast Cancer.  2015 Dec;18(4):339-346. 10.4048/jbc.2015.18.4.339.

Loss of Tumor Suppressor ARID1A Protein Expression Correlates with Poor Prognosis in Patients with Primary Breast Cancer

• Cho HD
• Lee JE
• Jung HY
• Oh MH
• Lee JH
• Jang SH
• Kim KJ
• Han SW
• Kim SY
• Kim HJ
• Bae SB
• Lee HJ

• KMID: 2176282
• DOI: http://doi.org/10.4048/jbc.2015.18.4.339

Abstract

PURPOSE
Somatic mutations of the chromatin remodeling AT-rich interactive domain 1A (SWI-like) gene (ARID1A) have been identified in many human cancers, including breast cancer. The purpose of this study was to evaluate the nuclear expression of ARID1A in breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance.
METHODS
IHC was performed on tissue microarrays of 476 cases of breast cancer. Associations between ARID1A expression and clinicopathologic characteristics and molecular subtype were retrospectively analyzed.
RESULTS
Low expression of ARID1A was found in 339 of 476 (71.2%) cases. Low expression of ARID1A significantly correlated with positive lymph node metastasis (p=0.027), advanced pathologic stage (p=0.001), low Ki-67 labeling index (p=0.003), and negative p53 expression (p=0.017). The ARID1A low expression group had significantly shorter disease-free and overall survival than the ARID1A high expression group (p<0.001 and p<0.001, respectively). Multivariate analysis demonstrated that low expression of ARID1A was a significant independent predictive factor for poor disease-free and overall survival in patients with breast cancer (disease-free survival: hazard ratio, 0.38, 95% confidence interval [CI], 0.20-0.73, p=0.004; overall survival: hazard ratio, 0.11, 95% CI, 0.03-0.46, p=0.003). In patients with luminal A type disease, patients with low ARID1A expression had significantly shorter disease-free and overall survival rates than patients with high ARID1A expression (p=0.022 and p=0.018, respectively).
CONCLUSION
Low expression of ARID1A is an independent prognostic factor for disease-free and overall survival in breast cancer patients and may be associated with luminal A type disease. Although the biologic function of ARID1A in breast cancer remains unknown, low expression of ARID1A can provide valuable prognostic information.

Keyword

ARID1A protein; Breast neoplasms; Immunohistochemistry; Prognosis

MeSH Terms

Breast Neoplasms*
Breast*
Chromatin Assembly and Disassembly
Humans
Immunohistochemistry
Lymph Nodes
Multivariate Analysis
Neoplasm Metastasis
Phenobarbital
Prognosis*
Retrospective Studies
Survival Rate
Phenobarbital

Figure

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  Figure 1 Immunohistochemical analyses of AT-rich interactive domain 1A (ARID1A) expression in breast cancer: (A) high and (B) low expression. ARID1A expressed in nuclei of the tumor cells (×400).

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  Figure 2 Kaplan-Meier survival curve for AT-rich interactive domain 1A (ARID1A). (A) Disease-free survival (p<0.001) and (B) overall survival (p<0.001) in breast cancer (n=476).

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  Figure 3 Kaplan-Meier survival curve for AT-rich interactive domain 1A (ARID1A) in patients with luminal A type disease (n=205). (A) Disease-free survival (p=0.022) and (B) overall survival (p=0.018).

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