ARID1A Expression and Association with Mismatch Repair Gene Status in Gastric Carcinomas
Keiyan Sy, Sara Hafezi-Bakhtiari, Streutker J Catherine, Clarke A Blaise. University of Toronto, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; St. Michael's Hospital, Toronto, ON, Canada
Background: ARID1A, a tumor suppressor gene is an important component of the multiprotein SW1/SNF chromatin remodeling complex which has multiple cellular functions including DNA repair. Loss of ARID1A has been described in gastric carcinoma(GC) and has been associated with poor outcome. In this study, we analyze expression of ARID1A and its correlation with mismatch repair gene (MMR) status and patients' clinical parameters in patients with GC.
Design: 113 resection specimens of invasive GC (2000-2011) were identified and a duplicate core tissue microarray (TMA) constructed. Tumor histomorphology and patient follow up data were retrieved. The TMA was interrogated for ARID1A and MMR protein (MLH1, MSH2, MSH6, and PMS2) expression.
Results: The mean patient age was 66.1 years and 31 patients were Asian. 19 /113 (16.9%) of the carcinomas were located in the proximal stomach. 25/113 (22.1%) patients were diagnosed as early Stage disease (T1). 61.1% of cases were intestinal-type carcinoma, 29.2% diffuse-type, 8.0% mixed carcinomas and 1.8% of cases were undifferentiated carcinomas. Follow-up data was available in 108/113 patients with a mean of 34 months (range: 1-128 months). 25/113 (22.1%) cases showed loss of expression of both MLH1 and PMS2 with a single case (0.9%) showing loss of both MSH2 and MSH6. 20/104 (19.3%) cases showed loss of ARID1A staining.(See Table 1) Loss of ARID1A expression was significantly associated with older age and loss of MLH1 expression. Patients with loss of ARID1A expression had a significantly worse mean survival (1.46 years) than those with normal expression (3.80 years). Multi-variate analysis indicates that tumor stage and ARID1A expression are independent prognostic factors in this patient cohort.
|ARID1 LOSS||ARID1 INTACT||P-VALUE|
|AGE (years+/-standard deviation)||72.6+/-3.0||64.4+/-1.5||0.016*|
|MEAN SURVIVAL (years+/-standard deviation)||1.46+/-0.21||3.53+/-0.20||0.004*|