TY - JOUR
T1 - Clinicopathological and Molecular Characterisation of Crohn's Disease-associated Small Bowel Adenocarcinomas
AU - Liao, Xiaoyan
AU - Li, Guangyuan
AU - McBride, Russel
AU - Houldsworth, Jane
AU - Harpaz, Noam
AU - Polydorides, Alexandros D.
N1 - Publisher Copyright:
Copyright © 2019 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].
PY - 2020/3/13
Y1 - 2020/3/13
N2 - Background and Aims: Small bowel adenocarcinoma [SBA] is a recognised complication of Crohn's disease [CD], but its low absolute prevalence limits opportunities for clinicopathological characterisation. Methods: We compared the clinical, pathological, and molecular features of 48 SBA from patients with CD [CDSBA] and 29 SBAs from patients without CD [NSBA] who underwent treatment at our tertiary care centre between 2000 and 2018. Results: Patients with CDSBA were younger than those with NSBA [mean age, 56 vs 64; p = 0.02]. Males predominated in both groups. Most CDSBA [69%] occurred in the ileum, whereas most NSBA occurred in the duodenum [38%] and jejunum [31%; p < 0.001]. Stage I tumours were more prevalent in the CDSBA [33% vs 3%; p = 0.002], although the rates of Stage IV disease and disease-specific mortality were similar in both groups. CDSBA were less likely to present a discrete mass [35% vs 93%; p < 0.001] and were more often stricturing or fistulising [75% vs 10%, respectively, p < 0.001] than NSBA. Microscopically, CDSBA were relatively heterogeneous, exhibiting at least three distinct growth patterns in 39% compared with 1% of NSBA [p = 0.01]. Low-grade tubuloglandular adenocarcinoma was the predominant pattern in 19% of CDSBA compared with 0% of NSBA [p = 0.003]. CDSBA were more frequently DNA mismatch repair proficient [90% vs 62%; p = 0.04] and exhibited profiles of frequently mutated genes similar to those of NSBA, except for IDH1 [18%] and SMAD4 [12%] mutations that occurred uniquely in CDSBA. Conclusions: These observations, based on the largest single-centre series described hitherto, establish that CDSBA is a distinct clinical, pathological, and molecular entity.
AB - Background and Aims: Small bowel adenocarcinoma [SBA] is a recognised complication of Crohn's disease [CD], but its low absolute prevalence limits opportunities for clinicopathological characterisation. Methods: We compared the clinical, pathological, and molecular features of 48 SBA from patients with CD [CDSBA] and 29 SBAs from patients without CD [NSBA] who underwent treatment at our tertiary care centre between 2000 and 2018. Results: Patients with CDSBA were younger than those with NSBA [mean age, 56 vs 64; p = 0.02]. Males predominated in both groups. Most CDSBA [69%] occurred in the ileum, whereas most NSBA occurred in the duodenum [38%] and jejunum [31%; p < 0.001]. Stage I tumours were more prevalent in the CDSBA [33% vs 3%; p = 0.002], although the rates of Stage IV disease and disease-specific mortality were similar in both groups. CDSBA were less likely to present a discrete mass [35% vs 93%; p < 0.001] and were more often stricturing or fistulising [75% vs 10%, respectively, p < 0.001] than NSBA. Microscopically, CDSBA were relatively heterogeneous, exhibiting at least three distinct growth patterns in 39% compared with 1% of NSBA [p = 0.01]. Low-grade tubuloglandular adenocarcinoma was the predominant pattern in 19% of CDSBA compared with 0% of NSBA [p = 0.003]. CDSBA were more frequently DNA mismatch repair proficient [90% vs 62%; p = 0.04] and exhibited profiles of frequently mutated genes similar to those of NSBA, except for IDH1 [18%] and SMAD4 [12%] mutations that occurred uniquely in CDSBA. Conclusions: These observations, based on the largest single-centre series described hitherto, establish that CDSBA is a distinct clinical, pathological, and molecular entity.
KW - Crohn's disease
KW - Small bowel adenocarcinoma
KW - next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=85081942090&partnerID=8YFLogxK
U2 - 10.1093/ecco-jcc/jjz135
DO - 10.1093/ecco-jcc/jjz135
M3 - Article
C2 - 31388669
AN - SCOPUS:85081942090
SN - 1873-9946
VL - 14
SP - 287
EP - 294
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
IS - 3
ER -