Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2015; 21(7): 2159-2168
Published online Feb 21, 2015. doi: 10.3748/wjg.v21.i7.2159
ARID1A expression in gastric adenocarcinoma: Clinicopathological significance and correlation with DNA mismatch repair status
Ryo Inada, Shigeki Sekine, Hirokazu Taniguchi, Hitoshi Tsuda, Hitoshi Katai, Toshiyoshi Fujiwara, Ryoji Kushima
Ryo Inada, Hirokazu Taniguchi, Hitoshi Tsuda, Ryoji Kushima, Pathology and Clinical Laboratory Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
Shigeki Sekine, Molecular Pathology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan
Ryo Inada, Toshiyoshi Fujiwara, Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
Hitoshi Katai, Gastric Surgery Division, National Cancer Center Hospital, Tokyo 104-0045, Japan
Author contributions: Inada R performed experiments and data analysis and wrote the manuscript; Sekine S designed the study, guided the experiments and wrote the manuscript; Taniguchi H, Tsuda H and Kushima R performed experiments and edited the manuscript; Katai H collected clinical samples and edited the manuscript; Fujiwara T edited the manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shigeki Sekine, MD, PhD, Molecular Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. ssekine@ncc.go.jp
Telephone: +81-3-35422511 Fax: +81-3-32482463
Received: June 28, 2014
Peer-review started: July 2, 2014
First decision: July 21, 2014
Revised: August 30, 2014
Accepted: September 29, 2014
Article in press: September 30, 2014
Published online: February 21, 2015
Processing time: 227 Days and 23.7 Hours
Abstract

AIM: To analyze the mismatch repair (MMR) status and the ARID1A expression as well as their clinicopathological significance in gastric adenocarcinomas.

METHODS: We examined the expressions of MMR proteins and ARID1A by immunohistochemistry in consecutive 489 primary gastric adenocarcinomas. The results were further correlated with clinicopathological variables.

RESULTS: The loss of any MMR protein expression, indicative of MMR deficiency, was observed in 38 cases (7.8%) and was significantly associated with an older age (68.6 ± 9.2 vs 60.4 ± 11.7, P < 0.001), a female sex (55.3% vs 31.3%, P = 0.004), an antral location (44.7% vs 25.7%, P = 0.021), and a differentiated histology (57.9% vs 39.7%, P = 0.023). Abnormal ARID1A expression, including reduced or loss of ARID1A expression, was observed in 109 cases (22.3%) and was significantly correlated with lymphatic invasion (80.7% vs 69.5%, P = 0.022) and lymph node metastasis (83.5% vs 73.7%, P = 0.042). The tumors with abnormal ARID1A expression more frequently indicated MMR deficiency (47.4% vs 20.2%, P < 0.001). A multivariate analysis identified abnormal ARID1A expression as an independent poor prognostic factor (HR = 1.36, 95%CI: 1.01-1.84; P = 0.040).

CONCLUSION: Our observations suggest that the AIRD1A inactivation is associated with lymphatic invasion, lymph node metastasis, poor prognosis, and MMR deficiency in gastric adenocarcinomas.

Keywords: Adenocarcinoma; ARID1A; Mismatch Repair; Stomach; Immunohistochemistry

Core tip: Inactivation of ARID1A, a key component of the chromatin remodeling complex, has been recently reported in several tumors, including gastric cancer. Previous studies showed a significant relationship between ARID1A mutations and MMR deficiency in gastric cancers. On the other hand, there have been inconsistent reports on the clinicopathological significance of altered ARID1A expression. In the present study, we examined expressions of ARID1A and MMR proteins in a large series of primary gastric adenocarcinomas, and showed their clinicopathological significance.