Aims

Loss of expression of mammalian SWI/SNF (BAF) complex subunits including SMARCA4, SMARCA2 and INI1/SMARCB1 (termed SWI/SNF deficiency) has been reported in colorectal carcinomas (CRCs) but its frequency and clinical significance is uncertain..

Methods and Results

We performed immunohistochemistry for SMARCA4, SMARCA2 and SMARCB1 on 4508 consecutive resected CRCs. SMARCA4 loss was found in 13 CRCs (0.3%), SMARCA2 in 59 (1.3%) and SMARCB1 in 21 (0.4%). Some CRCs showed loss of expression of more than one subunit, so that 84 CRCs (1.7%) were deficient for at least one component.

SWI/SNF deficiency was associated with higher-grade, right-sided location, mismatch repair deficiency (MMRd) and BRAFV600E mutation (p<0.05). 5.8% of MMRd and 5.4% of BRAFV600E-mutant cases were SWI/SNF deficient; compared to 0.9% and 0.4% of MMRp and BRAF wild-type cases, (p<0.001).

Any loss of expression of SMARCB1 and global loss of expression of SMARCA2 were associated with statistically significant worse overall survival, while SMARCA4 deficient CRCs demonstrated a trend only towards poor overall survival (p=0.121). In multivariate analysis, any loss of SMARCA4 and global loss of SMARCA2 were associated with worse survival (OR: 3.33; p=0.019 and OR: 3.39; p<0.001). Of particular note, among the subgroup of CRCs that were MMRd and BRAFV600E mutated (otherwise considered a good prognostic group) SMARCA4 loss was associated with much worse median survival (10.5 vs 110.9 months; p=0.003).

Conclusions

SWI/SNF deficiency is rare in CRC but enriched in MMRd tumors. Identifying these cases has morphologic associations and prognostic significance, and in the future may have potential therapeutic implications.