title: Altered expression of AT-rich interactive domain 1A in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Hongo 7-3-1, Tokyo 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Hongo 7-3-1, Tokyo 113-0033, Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Hongo 7-3-1, Tokyo 113-0033, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kunita
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo Hongo 7-3-1, Tokyo 113-0033, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo Hongo 7-3-1, Tokyo 113-0033, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Hongo 7-3-1, Tokyo 113-0033, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Shibahara
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo Hongo 7-3-1, Tokyo 113-0033, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo Hongo 7-3-1, Tokyo 113-0033, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis*; D016896:Treatment Outcome; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051176:beta Catenin / Q000032:analysis
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin
keywords: ARID1A; beta-catenin; hepatocellular carcinoma; immunohistochemistry; p53