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5. Small Bowel Carcinomas in Coeliac or Crohn’s Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium

Author

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

Subjects
Male, 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Oncology, Survival, Receptor, ErbB-2, Colorectal cancer, medicine.disease_cause, Inflammatory bowel disease, tumour-infiltrating lymphocyte, ErbB-2, 0302 clinical medicine, Crohn Disease, Retrospective Studie, Risk Factors, 80 and over, Child, Class I Phosphatidylinositol 3-Kinase, Aged, 80 and over, Colonic Neoplasm, Settore MED/12 - Gastroenterologia, Crohn's disease, MLH1 methylation, Tumour-infiltrating lymphocytes, Gastroenterology, General Medicine, Middle Aged, Prognosis, Microsatellite instability, MLH1 promoter methylation, 030220 oncology & carcinogenesis, Colonic Neoplasms, Survival Analysi, KRAS, Human, Receptor, Adult, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Prognosi, Class I Phosphatidylinositol 3-Kinases, Settore MED/08 - Anatomia Patologica, NO, Proto-Oncogene Proteins p21(ras), Young Adult, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, inflammatory bowel disease, microsatellite instability, survival, tumour-infiltrating lymphocytes, neoplasms, Aged, Retrospective Studies, Celiac Disease, Microsatellite Instability, Survival Analysis, Tumor Suppressor Protein p53, business.industry, Tumour-infiltrating lymphocyte, Risk Factor, Cancer, medicine.disease, eye diseases, digestive system diseases, 030104 developmental biology, business
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 cancer-specific 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.

Published
2017

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