Department of Breast Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, China.
Cancer Epidemiol. 2012 Jun;36(3):288-93. doi: 10.1016/j.canep.2011.07.006. Epub 2011 Sep 1.
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.
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.
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.
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.
ARID1A 基因编码 BAF250a，它是 ARID 家族 DNA 结合蛋白的成员之一，也是人类 SWI/SNF 相关复合物的一个亚基。ARID1A 的低表达与特定的肿瘤细胞系或特定的癌症组织的病理类型有关。本研究的目的是探讨 ARID1A 在浸润性导管乳腺癌中的表达，并评估其临床病理特征和预后价值。
采用实时逆转录聚合酶链反应（RT-PCR）法检测 40 对新鲜冷冻乳腺癌和正常乳腺组织中 ARID1A mRNA 的表达。采用免疫组织化学法检测 112 例浸润性乳腺癌石蜡包埋手术标本和 20 例匹配的正常乳腺组织中 BAF250a 的表达。我们进一步分析了 ARID1A 表达的临床病理特征。采用 Kaplan-Meier 法和 Cox 回归模型评估总生存时间。
乳腺癌组织中 ARID1A mRNA 的表达低于相应的正常组织（P<0.001），且这种低表达水平与肿瘤较大（P=0.038）、分期较高（P=0.016）、ER(-)（P=0.038）、Ki-67 较高（P=0.025）、P53 突变（P=0.018）和 ER(-)/PR(-)/Her-2(-)分子亚型（P=0.044）等因素显著相关。免疫组织化学染色显示，56%（63/112）的乳腺癌组织中存在低 BAF250a 表达。低 BAF250a 表达与肿瘤分期（P=0.021）、P53（P=0.018）、Ki-67（P=0.031）和 ER(-)/PR(-)/Her-2(-)分子亚型（P=0.044）显著相关。低 ARID1A 表达是总生存的预测因素，但不是独立因素。
这些数据表明，ARID1A 在乳腺癌中经常表达下调，我们需要进一步研究 ARID1A 和 SWI/SNF 复合物在乳腺癌发生中的作用，尤其是在三阴性乳腺癌中。
