Retrospective Study
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2014; 20(48): 18404-18412
Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18404
Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer
Xiao-Li Wei, De-Shen Wang, Shao-Yan Xi, Wen-Jing Wu, Dong-Liang Chen, Zhao-Lei Zeng, Rui-Yu Wang, Ya-Xin Huang, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu
Xiao-Li Wei, De-Shen Wang, Dong-Liang Chen, Zhao-Lei Zeng, Ying Jin, Feng Wang, Miao-Zhen Qiu, Hui-Yan Luo, Dong-Sheng Zhang, Rui-Hua Xu, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, Guangdong Province, China
Shao-Yan Xi, Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong Province, China
Wen-Jing Wu, Department of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, China
Rui-Yu Wang, Ya-Xin Huang, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Wei XL, Wang DS and Xi SY contributed equally to the study; Wei XL and Wang DS drafted the manuscript; Wei XL, Wang RY and Huang YX collected the clinical data of the colorectal cancer patients; Xi SY, Wu WJ, Wang DS and Zeng ZL performed the immunohistochemical staining; Wang F, Qiu MZ and Luo HY collected tumor slices; Xi SY and Zhang DS reviewed the pathologic slices and scored the immunohistochemical staining; Jin Y and Wang F performed the statistical analysis; Xu RH conceived, designed and coordinated the study, and offered help with preparation of the manuscript; all authors have read and approved the final manuscript.
Supported by National High Technology Research and Development Program of China (863 Program), No. 2012AA02A506; National Natural Science Foundation of China, No. 81372570; the Science and Technology Foundation of Guangdong Province, China, No. 2012B031800088; and the Science and Technology Foundation of Guangdong Province, China, No. C2011019
Correspondence to: Rui-Hua Xu, MD, PhD, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng Road East, Guangzhou 510060, Guangdong Province, China. xurh@sysucc.org.cn
Telephone: +86-20-87343468 Fax: +86-20-87343468
Received: May 21, 2014
Revised: June 29, 2014
Accepted: July 16, 2014
Published online: December 28, 2014
Processing time: 229 Days and 17.5 Hours
Abstract

AIM: To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.

METHODS: We retrospectively collected clinicopathologic data and archived paraffin-embedded primary colorectal cancer samples from 209 patients, including 111 patients with colon cancer and 98 patients with rectal cancer. The tumor stage ranged from stage I to stage IV according to the 7th edition of the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. All patients underwent resection of primary colorectal tumors. The expression of ARID1A protein in primary colorectal cancer tissues was examined by immunohistochemical staining. The clinicopathologic association and survival relevance of ARID1A protein loss in colorectal cancer were analyzed.

RESULTS: ARID1A loss by immunohistochemistry was not rare in primary colorectal cancer tumors (25.8%). There were 7.4%, 24.1%, 22.2% and 46.3% of patients with ARID1A loss staged at TNM stage I, II, III and IV, respectively, compared with 20.0%, 22.6%, 27.7% and 29.7% of patients without ARID1A loss staged at TNM stage I, II, III and IV, respectively. In patients with ARID1A loss, the distant metastasis rate was 46.3%. However, only 29.7% of patients without ARID1A loss were found to have distant metastasis. In terms of pathologic differentiation, there were 25.9%, 66.7% and 7.4% with poorly, moderately and well differentiated tumors in patients with ARID1A loss, and 14.2%, 72.3% and 13.5% with poorly, moderately and well differentiated tumors in patients without ARID1A loss, respectively. ARID1A loss was associated with late TNM stage (P = 0.020), distant metastasis (P = 0.026), and poor pathological classification (P = 0.035). However, patients with positive ARID1A had worse overall survival compared to those with negative ARID1A in stage IV colorectal cancer (HR = 2.49, 95%CI: 1.13-5.51).

CONCLUSION: ARID1A protein loss is associated with clinicopathologic characteristics in colorectal cancer patients and with survival in stage IV patients.

Keywords: AT-rich interactive domain 1A; Switching defective/sucrose non-fermenting complexes; Colorectal cancer; Clinicopathologic characteristics; Prognosis

Core tip: AT-rich interactive domain 1A (ARID1A) (BAF250A) is a member of the switching defective/sucrose non-fermenting (BAF) complexes, which remodel nucleosomes. ARID1A gene mutation and protein loss have been detected in many human cancers. However, research on their clinical association in colorectal cancer is limited and requires further exploration. We found that ARID1A loss was not rare in primary colorectal cancer tumors (25.8%), and it was associated with clinicopathologic characteristics in colorectal cancer patients and with survival in stage IV patients.