TY - JOUR
T1 - ARID1A expression loss in gastric cancer
T2 - Pathway-dependent roles with and without Epstein-Barr virus infection and microsatellite instability
AU - Abe, Hiroyuki
AU - Maeda, Daichi
AU - Hino, Rumi
AU - Otake, Yuya
AU - Isogai, Maya
AU - Ushiku, Aya Shinozaki
AU - Matsusaka, Keisuke
AU - Kunita, Akiko
AU - Ushiku, Tetsuo
AU - Uozaki, Hiroshi
AU - Tateishi, Yoko
AU - Hishima, Tsunekazu
AU - Iwasaki, Yoshiaki
AU - Ishikawa, Shumpei
AU - Fukayama, Masashi
PY - 2012/10
Y1 - 2012/10
N2 - The AT-rich interactive domain 1A gene (ARID1A), which encodes one of the subunits in the Switch/Sucrose Nonfermentable chromatin remodeling complex, carries mutations and is responsible for loss of protein expression in gastric carcinoma, particularly with Epstein-Barr virus (EBV) infection and a microsatellite instability-high phenotype. We used immunohistochemistry to investigate the significance of ARID1A loss in 857 gastric carcinoma cases, including 67 EBV(+) and 136 MLH1-lost gastric carcinomas (corresponding to a microsatellite instability-high phenotype). Loss of ARID1A expression was significantly more frequent in EBV(+) (23/67; 34 %) and MLH1-lost (40/136; 29 %) gastric carcinomas than in EBV(-)MLH1-preserved (32/657; 5 %) gastric carcinomas (P<0.01). Loss of ARID1A correlated with larger tumor size, advanced invasion depth, lymph node metastasis, and poor prognosis in EBV(-)MLH1-preserved gastric carcinoma. A correlation was found only with tumor size and diffuse-type histology in MLH1-lost gastric carcinoma, but no correlation was observed in EBV(+) gastric carcinoma. Loss of ARID1A expression in EBV(+) gastric carcinoma was highly frequent in the early stage of gastric carcinoma, although EBV infection did not cause downregulation of ARID1A: EBV-positive nasopharyngeal carcinomas (n=8) and lymphomas (n=15) failed to show loss of ARID1A, and EBV infection did not cause loss of ARID1A in gastric carcinoma cell lines. Taken together, loss of ARID1A may be an early change in carcinogenesis and may precede EBV infection in gastric epithelial cells, while loss of ARID1A promotes cancer progression in gastric cancer cells without EBV infection or loss of MLH1 expression. Loss of ARID1A has different and pathwaydependent roles in gastric carcinoma.
AB - The AT-rich interactive domain 1A gene (ARID1A), which encodes one of the subunits in the Switch/Sucrose Nonfermentable chromatin remodeling complex, carries mutations and is responsible for loss of protein expression in gastric carcinoma, particularly with Epstein-Barr virus (EBV) infection and a microsatellite instability-high phenotype. We used immunohistochemistry to investigate the significance of ARID1A loss in 857 gastric carcinoma cases, including 67 EBV(+) and 136 MLH1-lost gastric carcinomas (corresponding to a microsatellite instability-high phenotype). Loss of ARID1A expression was significantly more frequent in EBV(+) (23/67; 34 %) and MLH1-lost (40/136; 29 %) gastric carcinomas than in EBV(-)MLH1-preserved (32/657; 5 %) gastric carcinomas (P<0.01). Loss of ARID1A correlated with larger tumor size, advanced invasion depth, lymph node metastasis, and poor prognosis in EBV(-)MLH1-preserved gastric carcinoma. A correlation was found only with tumor size and diffuse-type histology in MLH1-lost gastric carcinoma, but no correlation was observed in EBV(+) gastric carcinoma. Loss of ARID1A expression in EBV(+) gastric carcinoma was highly frequent in the early stage of gastric carcinoma, although EBV infection did not cause downregulation of ARID1A: EBV-positive nasopharyngeal carcinomas (n=8) and lymphomas (n=15) failed to show loss of ARID1A, and EBV infection did not cause loss of ARID1A in gastric carcinoma cell lines. Taken together, loss of ARID1A may be an early change in carcinogenesis and may precede EBV infection in gastric epithelial cells, while loss of ARID1A promotes cancer progression in gastric cancer cells without EBV infection or loss of MLH1 expression. Loss of ARID1A has different and pathwaydependent roles in gastric carcinoma.
KW - ARID1A
KW - Epstein-Barr virus
KW - Gastric cancer
KW - Microsatellite instability
KW - MLH1
UR - http://www.scopus.com/inward/record.url?scp=84867403968&partnerID=8YFLogxK
U2 - 10.1007/s00428-012-1303-2
DO - 10.1007/s00428-012-1303-2
M3 - 記事
C2 - 22915242
AN - SCOPUS:84867403968
SN - 0945-6317
VL - 461
SP - 367
EP - 377
JO - Virchows Archiv
JF - Virchows Archiv
IS - 4
ER -