LAUSR

The switch/sucrose-nonfermenting (SWI/SNF) nucleosome complex consists of several proteins that are involved in cellular proliferation and tumor suppression. The aim of this study was to correlate immunohistochemical expression of four SWI/SNF complex subunits, SMARCA2, SMARCB1, SMARCA4, and ARID1A, with clinicopathologic and molecular features and patient survival in 338 patients with colorectal adenocarcinoma using a tissue microarray approach. Twenty-three (7%) colorectal adenocarcinomas demonstrated deficient SWI/SNF expression: 7 had SMARCA2 deficiency, 12 had ARID1A deficiency, and 4 had both SMARCA2 and ARID1A deficiency. No cases were SMARCB1 or SMARCA4-deficient. Twelve (52%) SWI/SNF complex-deficient tumors demonstrated MMR deficiency (p=0.02), 6 (26%) showed medullary differentiation (p=0.001), and 9 were negative for CDX2 expression (p<0.001). Among the MMR deficient SWI/SNF complex-deficient tumors, 8 were sporadic MLH1 deficient and 4 were seen in Lynch syndrome patients. Compared to ARID1A-deficient alone tumors, SMARCA2-deficient tumors were less likely to exhibit MMR deficiency (27% vs. 75%, p=0.04), medullary differentiation (0% vs. 50%, p=0.01), and mucinous differentiation (0% vs. 42%, p=0.04). Conventional gland-forming histology was more often identified in SMARCA2-deficient tumors (11/11, 100%) compared to tumors with ARID1A deficiency alone (4/12, 33%) (p=0.001). There was no difference in KRAS mutation, BRAF mutation, stage, disease-specific survival, or disease-free survival for patients stratified by SWI/SNF expression (all with p>0.05). In conclusion, SMARCA2-deficient and ARID1A-deficient colorectal carcinomas had distinctly different clinicopathologic features with ARID1A-deficient tumors exhibiting medullary and mucinous differentiation and MMR deficiency, and SMARCA2-deficient tumors demonstrating conventional gland-forming histologic growth with less frequent MMR deficiency.