Switch/sucrose nonfermenting nucleosome complex–deficient colorectal carcinomas have distinct clinicopathologic features

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 mismatch repair (MMR) deficiency (p = 0.02), 6 (26%) showed medullary differentiation (p = 0.001), and 9 were negative for CDX2 expression (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.