Frequent low expression of chromatin remodeling gene ARID1A in breast cancer and its clinical significance

Abstract

Background: ARID1A gene encodes BAF250a which is a member of the ARID family of DNA-binding proteins and a subunit of human SWI/SNF-related complexes. Low expression of ARID1A has been correlated with specific tumor cell lines or specific pathological types of cancer tissue. The purpose of this study was to investigate the expression of ARID1A in invasive ductal breast carcinomas and to evaluate its clinicopathological characteristics and prognostic value.

Methods: ARID1A mRNA expression was evaluated by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 40 pairs of fresh frozen breast cancer and normal breast samples. BAF250a expression was evaluated by immunohistochemistry in 112 paraffin-embedded surgical specimens of invasive breast cancers and 20 cases of matched normal breast tissues. We further analyzed the clinicopathological characteristics of ARID1A expression. Overall survival time was assessed by the Kaplan-Meier method and Cox regression model.

Results: ARID1A mRNA expression was lower in breast cancer tissue than in corresponding normal tissue (P<0.001), and this decreased expression level was markedly associated with factors such as larger tumor size (P=0.038), higher stage (P=0.016), ER(-) (P=0.038), higher Ki-67 (P=0.025), P53 mutation (P=0.018) and ER(-)/PR(-)/Her-2(-) molecular subtype (P=0.044). With immunohistochemical staining, we showed that low BAF250a expression existed in 56% (63/112) of the breast cancers tissues. Low BAF250a expression was significantly associated with tumor stage (P=0.021), P53 (P=0.018), Ki-67 (P=0.031) and ER(-)/PR(-)/Her-2(-) molecular subtype (P=0.044). Low ARID1A expression was a predictor, not an independent, of overall survival.

Conclusion: These data suggest that low ARID1A expression is frequent in breast cancers, and we need to investigate further the role of ARID1A and SWI/SNF complexes in breast tumorigenesis, especially in triple-negative breast cancer.