Loss of ARID1A expression in colorectal carcinoma is strongly associated with mismatch repair deficiency.
ARID1A is a tumor suppressor gene involved in chromatin remodelling. ARID1A mutations and loss of protein expression occur commonly in endometrioid and gynecological clear cell carcinoma where they are associated with mismatch repair (MMR) deficiency. We assessed ARID1A expression in a large cohort of colorectal carcinomas (CRCs). Immunohistochemistry for ARID1A was performed on whole sections from 100 CRCs and on 1876 CRCs in tissue microarray format. There was complete concordance between the staining on whole slides and tissue microarray sections. Loss of staining was found in 110 (5.9%) of 1876 CRCs and was strongly associated with older age, right sided location, large size, BRAF V600E mutation, MMR deficiency, high histological grade and medullary morphology, (all P < .01). There was a trend towards loss of expression being more common in females (P = .06). When subclassified by combined BRAF V600E mutation and MMR status, loss of ARID1A expression was found most commonly in CRCs with the BRAF V600E mutated, MMR- deficient phenotype (58 of 232 cases, 25%, P < .01). In univariate and multivariate analysis, loss of ARID1A expression was not associated with overall survival-hazard ratio 1.05 (0.68-1.64) and 0.60 (0.24-1.44), respectively. All carcinomas arising in patients with known Lynch syndrome (n = 12) were ARID1A positive. We conclude that loss of ARID1A expression occurs in a small but significant proportion of CRCs where it is strongly correlated with mismatch repair deficiency and other clinical and pathological features associated with somatic hypermethylation.
['Chou|Angela|A|', 'Toon|Christopher W|CW|', 'Clarkson|Adele|A|', 'Sioson|Loretta|L|', 'Houang|Michelle|M|', 'Watson|Nicole|N|', 'DeSilva|Keshani|K|', 'Gill|Anthony J|AJ|']
D000230:Adenocarcinoma D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D001932:Brain Neoplasms D015179:Colorectal Neoplasms D004268:DNA-Binding Proteins D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D009154:Mutation D009386:Neoplastic Syndromes, Hereditary D009687:Nuclear Proteins D048493:Proto-Oncogene Proteins B-raf D012737:Sex Factors D046888:Tissue Array Analysis D014157:Transcription Factors D055815:Young Adult
ARID1A Mismatch repair deficiency BAF250a Colon cancer Microsatellite instability