ARID1A/BAF250a as a prognostic marker for gastric carcinoma: a study of 2 cohorts.

Abstract

ARID1A/BAF250a has been recently implicated as a tumor suppressor in gastric cancer. We sought to clarify the clinical significance of BAF250a/ARID1A in relation to other clinical parameters and relevant biomarkers in gastric carcinoma. Cases from 2 separate cohorts of patients with gastric carcinoma from Vancouver (n = 173) and Toronto (n = 80) were selected for the construction of tissue microarrays, which were used to assess the immunohistochemical status of BAF250a (anti-ARID1A), mismatch repair proteins and p53, as well as in situ hybridization for HER2 amplification and Epstein-Barr virus infection. The Toronto cohort contained a higher proportion of early stage cases (P = .019) and a smaller proportion of cases from the proximal stomach (P < .001). Overall, immunohistochemical loss of BAF250a was observed in 22.5% of gastric adenocarcinomas from the Vancouver group and 20% from Toronto. In both cohorts, loss of BAF250a was positively associated with loss of mismatch repair protein expression (P < .0001 and P = .035, respectively). Loss of BAF250a expression was independently associated with poor overall survival in the Toronto cohort (P = .0015), whereas no significant association with survival was observed in the Vancouver cohort. BAF250a loss was not significantly associated with any additional clinical parameters in either cohort. HER2 amplification was confirmed as a negative prognostic factor in both cohorts. These findings suggest that ARID1A/BAF250a may be of prognostic significance in a subset of patients with early stage gastric cancer and that pathological assessment should increasingly use a multimarker approach.

• Authors: Kimberly C Wiegand, Keiyan Sy, Steve E Kalloger, Hector Li-Chang, Ryan Woods, Aalok Kumar, Catherine J Streutker, Sara Hafezi-Bakhtiari, Chen Zhou, Howard J Lim, David G Huntsman, Blaise Clarke, David F Schaeffer
• Journal: Human pathology (Hum Pathol) Vol. 45 Issue 6 Pg. 1258-68 (Jun 2014) ISSN: 1532-8392 [Electronic] United States
• PMID: 24767857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• ARID1A protein, human
• Biomarkers, Tumor
• DNA-Binding Proteins
• Nuclear Proteins
• Transcription Factors

Topics

• Adenocarcinoma (metabolism, mortality, pathology)
• Biomarkers, Tumor (analysis)
• Cohort Studies
• DNA-Binding Proteins
• Female
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Nuclear Proteins (analysis, biosynthesis)
• Prognosis
• Proportional Hazards Models
• Stomach Neoplasms (metabolism, mortality, pathology)
• Transcription Factors (analysis, biosynthesis)