Small bowel carcinomas in coeliac or Crohn's disease: Clinico-pathological, molecular, and prognostic features. A study from the small bowel cancer Italian consortium

A. Vanoli, A. Di Sabatino, D. Furlan, C. Klersy, F. Grillo, R. Fiocca, C. Mescoli, M. Rugge, G. Nesi, P. Fociani, G. Sampietro, S. Ardizzone, O. Luinetti, A. Calabrò, F. Tonelli, U. Volta, D. Santini, G. Caio, P. Giuffrida, L. ElliS. Ferrero, G. Latella, A. Ciardi, R. Caronna, G. Solina, A. Rizzo, C. Ciacci, F.P. D'Armiento, M. Salemme, V. Villanacci, R. Cannizzaro, V. Canzonieri, L.R. Bonetti, L. Biancone, G. Monteleone, A. Orlandi, G. Santeusanio, M.C. Macciomei, R. D'Incà, V. Perfetti, G. Sandri, M. Silano, A.M. Florena, A.G. Giannone, C. Papi, L. Coppola, P. Usai, A. Maccioni, M. Astegiano, P. Migliora, R. Manca, M. Martino, D. Trapani, R. Cerutti, P. Alberizzi, R. Riboni, F. Sessa, M. Paulli, E. Solcia, G.R. Corazza

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Aims: An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. Methods: A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. Results: CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancerspecific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI-which was the result of MLH1 promoter methylation in all but one cases-and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications. Conclusions: In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy. © 2017 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.
Original languageEnglish
Pages (from-to)942-953
Number of pages12
JournalJournal of Crohn's and Colitis
Volume11
Issue number8
DOIs
Publication statusPublished - 2017

Keywords

  • Inflammatory bowel disease
  • Microsatellite instability
  • MLH1 promoter methylation
  • Survival
  • Tumour-infiltrating lymphocytes
  • B Raf kinase
  • epidermal growth factor receptor 2
  • K ras protein
  • MutL protein homolog 1
  • protein p53
  • adult
  • aged
  • Article
  • cancer prognosis
  • cancer specific survival
  • celiac disease
  • child
  • cohort analysis
  • controlled study
  • Crohn disease
  • female
  • gene
  • gene amplification
  • HER2 gene
  • human
  • longitudinal study
  • major clinical study
  • male
  • microsatellite instability
  • middle aged
  • MLH1 gene
  • oncogene K ras
  • oncogene N ras
  • overall survival
  • PIK3CA gene
  • priority journal
  • promoter region
  • retrospective study
  • school child
  • small intestine carcinoma
  • tumor associated leukocyte
  • tumor suppressor gene
  • very elderly
  • young adult

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