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 journalArticle

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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

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Intestinal Neoplasms
Celiac Disease
Crohn Disease
Carcinoma
Microsatellite Instability
Tumor-Infiltrating Lymphocytes
Survival
erbB-2 Genes
Mutation
p53 Genes

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

Cite this

Small bowel carcinomas in coeliac or Crohn's disease: Clinico-pathological, molecular, and prognostic features. A study from the small bowel cancer Italian consortium. / Vanoli, A.; Di Sabatino, A.; Furlan, D.; Klersy, C.; Grillo, F.; Fiocca, R.; Mescoli, C.; Rugge, M.; Nesi, G.; Fociani, P.; Sampietro, G.; Ardizzone, S.; Luinetti, O.; Calabrò, A.; Tonelli, F.; Volta, U.; Santini, D.; Caio, G.; Giuffrida, P.; Elli, L.; Ferrero, S.; Latella, G.; Ciardi, A.; Caronna, R.; Solina, G.; Rizzo, A.; Ciacci, C.; D'Armiento, F.P.; Salemme, M.; Villanacci, V.; Cannizzaro, R.; Canzonieri, V.; Bonetti, L.R.; Biancone, L.; Monteleone, G.; Orlandi, A.; Santeusanio, G.; Macciomei, M.C.; D'Incà, R.; Perfetti, V.; Sandri, G.; Silano, M.; Florena, A.M.; Giannone, A.G.; Papi, C.; Coppola, L.; Usai, P.; Maccioni, A.; Astegiano, M.; Migliora, P.; Manca, R.; Martino, M.; Trapani, D.; Cerutti, R.; Alberizzi, P.; Riboni, R.; Sessa, F.; Paulli, M.; Solcia, E.; Corazza, G.R.

In: Journal of Crohn's and Colitis, Vol. 11, No. 8, 2017, p. 942-953.

Research output: Contribution to journalArticle

Vanoli, A, Di Sabatino, A, Furlan, D, Klersy, C, Grillo, F, Fiocca, R, Mescoli, C, Rugge, M, Nesi, G, Fociani, P, Sampietro, G, Ardizzone, S, Luinetti, O, Calabrò, A, Tonelli, F, Volta, U, Santini, D, Caio, G, Giuffrida, P, Elli, L, Ferrero, S, Latella, G, Ciardi, A, Caronna, R, Solina, G, Rizzo, A, Ciacci, C, D'Armiento, FP, Salemme, M, Villanacci, V, Cannizzaro, R, Canzonieri, V, Bonetti, LR, Biancone, L, Monteleone, G, Orlandi, A, Santeusanio, G, Macciomei, MC, D'Incà, R, Perfetti, V, Sandri, G, Silano, M, Florena, AM, Giannone, AG, Papi, C, Coppola, L, Usai, P, Maccioni, A, Astegiano, M, Migliora, P, Manca, R, Martino, M, Trapani, D, Cerutti, R, Alberizzi, P, Riboni, R, Sessa, F, Paulli, M, Solcia, E & Corazza, GR 2017, 'Small bowel carcinomas in coeliac or Crohn's disease: Clinico-pathological, molecular, and prognostic features. A study from the small bowel cancer Italian consortium', Journal of Crohn's and Colitis, vol. 11, no. 8, pp. 942-953. https://doi.org/10.1093/ecco-jcc/jjx031
Vanoli, A. ; Di Sabatino, A. ; Furlan, D. ; Klersy, C. ; Grillo, F. ; Fiocca, R. ; Mescoli, C. ; Rugge, M. ; Nesi, G. ; Fociani, P. ; Sampietro, G. ; Ardizzone, S. ; Luinetti, O. ; Calabrò, A. ; Tonelli, F. ; Volta, U. ; Santini, D. ; Caio, G. ; Giuffrida, P. ; Elli, L. ; Ferrero, S. ; Latella, G. ; Ciardi, A. ; Caronna, R. ; Solina, G. ; Rizzo, A. ; Ciacci, C. ; D'Armiento, F.P. ; Salemme, M. ; Villanacci, V. ; Cannizzaro, R. ; Canzonieri, V. ; Bonetti, L.R. ; Biancone, L. ; Monteleone, G. ; Orlandi, A. ; Santeusanio, G. ; Macciomei, M.C. ; D'Incà, R. ; Perfetti, V. ; Sandri, G. ; Silano, M. ; Florena, A.M. ; Giannone, A.G. ; Papi, C. ; Coppola, L. ; Usai, P. ; Maccioni, A. ; Astegiano, M. ; Migliora, P. ; Manca, R. ; Martino, M. ; Trapani, D. ; Cerutti, R. ; Alberizzi, P. ; Riboni, R. ; Sessa, F. ; Paulli, M. ; Solcia, E. ; Corazza, G.R. / Small bowel carcinomas in coeliac or Crohn's disease: Clinico-pathological, molecular, and prognostic features. A study from the small bowel cancer Italian consortium. In: Journal of Crohn's and Colitis. 2017 ; Vol. 11, No. 8. pp. 942-953.
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title = "Small bowel carcinomas in coeliac or Crohn's disease: Clinico-pathological, molecular, and prognostic features. A study from the small bowel cancer Italian consortium",
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. {\circledC} 2017 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.",
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",
author = "A. Vanoli and {Di Sabatino}, A. and D. Furlan and C. Klersy and F. Grillo and R. Fiocca and C. Mescoli and M. Rugge and G. Nesi and P. Fociani and G. Sampietro and S. Ardizzone and O. Luinetti and A. Calabr{\`o} and F. Tonelli and U. Volta and D. Santini and G. Caio and P. Giuffrida and L. Elli and S. Ferrero and G. Latella and A. Ciardi and R. Caronna and G. Solina and A. Rizzo and C. Ciacci and F.P. D'Armiento and M. Salemme and V. Villanacci and R. Cannizzaro and V. Canzonieri and L.R. Bonetti and L. Biancone and G. Monteleone and A. Orlandi and G. Santeusanio and M.C. Macciomei and R. D'Inc{\`a} and V. Perfetti and G. Sandri and M. Silano and A.M. Florena and A.G. Giannone and C. Papi and L. Coppola and P. Usai and A. Maccioni and M. Astegiano and P. Migliora and R. Manca and M. Martino and D. Trapani and R. Cerutti and P. Alberizzi and R. Riboni and F. Sessa and M. Paulli and E. Solcia and G.R. Corazza",
note = "Cited By :3 Export Date: 20 February 2018 Correspondence Address: Di Sabatino, A.; Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Universit{\`a} di Pavia, Piazzale Golgi 19, Italy; email: a.disabatino@smatteo.pv.it",
year = "2017",
doi = "10.1093/ecco-jcc/jjx031",
language = "English",
volume = "11",
pages = "942--953",
journal = "Journal of Crohn's and Colitis",
issn = "1873-9946",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Small bowel carcinomas in coeliac or Crohn's disease: Clinico-pathological, molecular, and prognostic features. A study from the small bowel cancer Italian consortium

AU - Vanoli, A.

AU - Di Sabatino, A.

AU - Furlan, D.

AU - Klersy, C.

AU - Grillo, F.

AU - Fiocca, R.

AU - Mescoli, C.

AU - Rugge, M.

AU - Nesi, G.

AU - Fociani, P.

AU - Sampietro, G.

AU - Ardizzone, S.

AU - Luinetti, O.

AU - Calabrò, A.

AU - Tonelli, F.

AU - Volta, U.

AU - Santini, D.

AU - Caio, G.

AU - Giuffrida, P.

AU - Elli, L.

AU - Ferrero, S.

AU - Latella, G.

AU - Ciardi, A.

AU - Caronna, R.

AU - Solina, G.

AU - Rizzo, A.

AU - Ciacci, C.

AU - D'Armiento, F.P.

AU - Salemme, M.

AU - Villanacci, V.

AU - Cannizzaro, R.

AU - Canzonieri, V.

AU - Bonetti, L.R.

AU - Biancone, L.

AU - Monteleone, G.

AU - Orlandi, A.

AU - Santeusanio, G.

AU - Macciomei, M.C.

AU - D'Incà, R.

AU - Perfetti, V.

AU - Sandri, G.

AU - Silano, M.

AU - Florena, A.M.

AU - Giannone, A.G.

AU - Papi, C.

AU - Coppola, L.

AU - Usai, P.

AU - Maccioni, A.

AU - Astegiano, M.

AU - Migliora, P.

AU - Manca, R.

AU - Martino, M.

AU - Trapani, D.

AU - Cerutti, R.

AU - Alberizzi, P.

AU - Riboni, R.

AU - Sessa, F.

AU - Paulli, M.

AU - Solcia, E.

AU - Corazza, G.R.

N1 - Cited By :3 Export Date: 20 February 2018 Correspondence Address: Di Sabatino, A.; Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Piazzale Golgi 19, Italy; email: a.disabatino@smatteo.pv.it

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Inflammatory bowel disease

KW - Microsatellite instability

KW - MLH1 promoter methylation

KW - Survival

KW - Tumour-infiltrating lymphocytes

KW - B Raf kinase

KW - epidermal growth factor receptor 2

KW - K ras protein

KW - MutL protein homolog 1

KW - protein p53

KW - adult

KW - aged

KW - Article

KW - cancer prognosis

KW - cancer specific survival

KW - celiac disease

KW - child

KW - cohort analysis

KW - controlled study

KW - Crohn disease

KW - female

KW - gene

KW - gene amplification

KW - HER2 gene

KW - human

KW - longitudinal study

KW - major clinical study

KW - male

KW - microsatellite instability

KW - middle aged

KW - MLH1 gene

KW - oncogene K ras

KW - oncogene N ras

KW - overall survival

KW - PIK3CA gene

KW - priority journal

KW - promoter region

KW - retrospective study

KW - school child

KW - small intestine carcinoma

KW - tumor associated leukocyte

KW - tumor suppressor gene

KW - very elderly

KW - young adult

U2 - 10.1093/ecco-jcc/jjx031

DO - 10.1093/ecco-jcc/jjx031

M3 - Article

VL - 11

SP - 942

EP - 953

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 8

ER -