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

Antonino Giulio Giannone, Ada Maria Florena, Livia Biancone, Antonio Calabrò, Luca Reggiani Bonetti, Rachele Manca, Catherine Klersy, Giovanni Monteleone, Giacomo Caio, Aroldo Rizzo, Alessandro Vanoli, Paolo Giuffrida, Federica Grillo, Vincenzo Villanacci, Marianna Salemme, Paolo Usai, Michele Martino, Davide Trapani, Giuseppe Santeusanio, Gino R. CorazzaAntonio Maccioni, Roberta Cerutti, Maria C. Macciomei, Claudia Mescoli, Paola Migliora, Gaspare Solina, Luca Elli, Roberto Caronna, Paolo Fociani, Roberta Riboni, Marco Silano, Antonio Di Sabatino, Renato Cannizzaro, Ombretta Luinetti, Giovanni Latella, Marco Astegiano, Daniela Furlan, Vittorio Perfetti, Claudio Papi, Gabriella Nesi, Vincenzo Canzonieri, Gianluca Sampietro, Renata D'Incà, Enrico Solcia, Antonio Ciardi, Massimo Rugge, Carolina Ciacci, Marco Paulli, Sandro Ardizzone, Luigi Coppola, Giancarlo Sandri, Umberto Volta, Francesco Tonelli, Augusto Orlandi, Fausto Sessa, Roberto Fiocca, Francesco P. D'Armiento, Stefano Ferrero, Donatella Santini, Paola Alberizzi

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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.
Lingua originaleEnglish
pagine (da-a)942-953
Numero di pagine12
RivistaJournal of Crohn's and Colitis
Volume11
Stato di pubblicazionePublished - 2017

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All Science Journal Classification (ASJC) codes

  • Gastroenterology

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Giannone, A. G., Florena, A. M., Biancone, L., Calabrò, A., Bonetti, L. R., Manca, R., Klersy, C., Monteleone, G., Caio, G., Rizzo, A., Vanoli, A., Giuffrida, P., Grillo, F., Villanacci, V., Salemme, M., Usai, P., Martino, M., Trapani, D., Santeusanio, G., ... Alberizzi, P. (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, 11, 942-953.