ARID1A/BAF250a as a prognostic marker for gastric carcinoma: a study of 2 cohorts.
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.
The Biomedical Research Center, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
Kimberly C
KC
Wiegand
Department of Pathology, University Health Network, Toronto, Ontario, M5G 2C4, Canada.
Keiyan
K
Sy
Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, V6T 2B5, Canada; The University of British Columbia (UBC), Vancouver, British Columbia, V6T 1Z4, Canada.
Steve E
SE
Kalloger
The University of British Columbia (UBC), Vancouver, British Columbia, V6T 1Z4, Canada.
Hector
H
Li-Chang
Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 4E6, Canada.
Ryan
R
Woods
Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 4E6, Canada.
Aalok
A
Kumar
Department of Pathology, St Michael's Hospital, Toronto, Ontario, M5B 1W8, Canada.
Catherine J
CJ
Streutker
Department of Pathology, University Health Network, Toronto, Ontario, M5G 2C4, Canada.
Sara
S
Hafezi-Bakhtiari
Department of Pathology, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 4E6, Canada.
Chen
C
Zhou
Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 4E6, Canada.
Howard J
HJ
Lim
The University of British Columbia (UBC), Vancouver, British Columbia, V6T 1Z4, Canada; Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 4E6, Canada; Genetic Pathology Evaluation Centre of the Prostate Research Centre, Vancouver General Hospital, Vancouver, British Columbia, V6H 3Z6, Canada; Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 4E6, Canada.
David G
DG
Huntsman
Department of Pathology, University Health Network, Toronto, Ontario, M5G 2C4, Canada.
Blaise
B
Clarke
Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, V6T 2B5, Canada; The University of British Columbia (UBC), Vancouver, British Columbia, V6T 1Z4, Canada. Electronic address: david.schaeffer@vch.ca.
David F
DF
Schaeffer
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015331:Cohort Studies; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*
C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
ARID1A; BAF250a; Gastric cancer; Microsatellite instability; SWI/SNF