Altered expression of AT-rich interactive domain 1A in hepatocellular carcinoma.
Altered expression of AT-rich interactive domain 1A in hepatocellular carcinoma.
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发表时间：
2015-03
影响因子：
1.4
通讯作者：
Hiroyuki Abe;Akimasa Hayashi;A. Kunita;Y. Sakamoto;K. Hasegawa;J. Shibahara;N. Kokudo;M. Fukayama
中科院分区：
文献类型：
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作者：
Hiroyuki Abe;Akimasa Hayashi;A. Kunita;Y. Sakamoto;K. Hasegawa;J. Shibahara;N. Kokudo;M. Fukayama
富含AT的相互作用结构域1A（ARID 1A）是Switch/Sucrose non-fermentable（SWI/SNF）染色质重塑复合物的亚基。近年来，全基因组全外显子测序发现肝细胞癌中ARID 1A基因突变频繁，但ARID 1A基因突变的临床病理意义尚未明确。本研究采用免疫组化方法检测了290例肝细胞癌中ARID 1A的表达。在组织微阵列的评估中，ARID 1A改变的病例（总共63例，21.7%）包括11例（3.8%）表达缺失和52例（17.9%）弱表达。ARID 1A的表达与肿瘤大小（P=0.034）和肿瘤组织学分化程度（P=0.035）有关。与年龄、性别、肝硬化、TNM分期、肿瘤大小、肿瘤数量、血管侵犯、患者生存率、HBV感染、HCV感染、大量饮酒和糖尿病无显著相关性。11例ARID 1A基因缺失者EBER原位杂交均为阴性。ARID 1A的表达改变与p53（P=0.018）或β-连环蛋白（P=0.025）的核表达呈负相关。ARID 1A的改变在每个病例中存在一定的异质性，整个切片的免疫组化显示，在TMA分析中ARID 1A缺失的11例病例中，有4例在肿瘤内显示局部阳性区域。ARID 1A的改变可能加速肝细胞癌亚群中的肿瘤生长，并且该途径可能不同于p53和β-连环蛋白途径。
AT-rich interactive domain 1A (ARID1A) is a subunit of the Switch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complex. Recently, genome-wide whole exome sequencing revealed frequent mutations of ARID1A in hepatocellular carcinoma, but clinicopathological significance of ARID1A alteration has not been clarified yet. In this study, expression of ARID1A was investigated immunohistochemically in 290 cases of hepatocellular carcinomas. In the evaluation of tissue microarrays, cases of ARID1A alteration (63 total cases, 21.7%) consisted of 11 (3.8%) cases showing loss of expression and 52 (17.9%) with weak expression. Alteration of ARID1A was correlated with larger tumor size (P=0.034) and well or moderate differentiation of tumor histology (P=0.035). There was no significant correlation with age, sex, cirrhosis, TNM stage, tumor size, number of tumors, vascular invasion, patient survival, HBV infection, HCV infection, heavy use of alcohol, nor diabetes mellitus. EBER in situ hybridization was negative in all 11 cases with loss of ARID1A. Altered expression of ARID1A was inversely correlated with nuclear expression of p53 (P=0.018) or beta-catenin (P=0.025). There was some heterogeneity of ARID1A alteration within each case, and immunohistochemistry of the whole sections demonstrated that four of 11 cases with loss of ARID1A in TMA analysis showed localized positive area within the tumor. Alteration of ARID1A may accelerate tumor growth in a subset of hepatocellular carcinoma, and this pathway may be distinct from p53 and beta-catenin pathways.