Switch/sucrose-non-fermentable (SWI/SNF) complex (SMARCA4, SMARCA2, INI1/SMARCB1)-deficient colorectal carcinomas are strongly associated with microsatellite instability: an incidence study in 4508 colorectal carcinomas.
BAF complex
INI1
SMARCA2
SMARCA4
SMARCB1
SWI/SNF chromatin remodelling complex
colorectal carcinoma
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
May 2022
May 2022
Historique:
revised:
28
11
2021
received:
01
10
2021
accepted:
21
12
2021
pubmed:
25
12
2021
medline:
20
4
2022
entrez:
24
12
2021
Statut:
ppublish
Résumé
Loss of expression of mammalian switch/sucrose-non-fermentable (SWI/SNF) [BRG1/BRM-associated factor (BAF)] complex subunits, including SMARCA4, SMARCA2 and INI1/SMARCB1 (termed SWI/SNF complex deficiency), has been reported in colorectal carcinomas (CRCs) but its frequency and clinical significance are uncertain. We performed immunohistochemistry for SMARCA4, SMARCA2 and SMARCB1 on 4508 consecutive resected CRCs. Loss of SMARCA4 expression was found in 13 cases (0.3%), loss of SMARCA2 expression was found in 59 cases (1.3%), and loss of SMARCB1 expression was found in 21 cases (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 complex deficiency was associated with higher grade, a right-sided location, mismatch repair deficiency, and BRAF V600E mutation (P < 0.05); 5.8% of mismatch repair-deficient (MMRd) cases and 5.4% of BRAF V600E-mutant cases were SWI/SNF complex-deficient, as compared with 0.9% and 0.4% of mismatch repair-proficient and BRAF-wild-type cases (P < 0.001). Any loss of SMARCB1 expression and global loss of SMARCA2 expression were associated with statistically significant worse overall survival, whereas SMARCA4-deficient cases showed a trend only towards poor overall survival (P = 0.121). In multivariate analysis, any loss of SMARCA4 expression and global loss of SMARCA2 expression were associated with worse survival [odds ratio (OR) 3.33, P = 0.019; and OR 3.39, P < 0.001]. Of particular note, among the subgroup of cases that were MMRd and BRAF V600E-mutated (otherwise considered to be a good prognostic group), loss of SMARCA4 expression was associated with much worse median survival (10.5 months versus 110.9 months; P = 0.003). SWI/SNF complex deficiency is rare in CRC but is enriched in MMRd cases. Identifying these cases has morphological associations and prognostic significance, and in the future may have potential therapeutic implications.
Substances chimiques
Nuclear Proteins
0
SMARCA2 protein, human
0
SMARCB1 Protein
0
SMARCB1 protein, human
0
Transcription Factors
0
Sucrose
57-50-1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
SMARCA4 protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
906-921Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 John Wiley & Sons Ltd.
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