Small bowel carcinomas in celiac or Crohn's disease: Distinctive histophenotypic, molecular and histogenetic patterns
| Autor: | Vanoli, A., Di Sabatino, A., Martino, M., Klersy, C., Grillo, F., Mescoli, C., Nesi, G., Volta, U., Fornino, D., Luinetti, O., Fociani, P., Villanacci, V., D'Armiento, F. P., Cannizzaro, R., Latella, G., Ciacci, C., Biancone, L., Paulli, M., Sessa, F., Rugge, M., Fiocca, R., Corazza, G. R., Solcia, E., Ardizzone, S., Astegiano, M., Caio, G., Calabro, A., Canzonieri, V., Cerutti, R., Ciardi, A., Coppola, L., D'Inca, R., Elli, L., Ferrero, S., Florena, A. M., Furlan, D., Giannone, A. G., Giuffrida, P., Macciomei, M. C., Maccioni, A., Monteleone, G., Migliora, P., Orlandi, A., Papi, C., Perfetti, V., Bonetti, L. R., Rizzo, A., Salemme, M., Sandri, G., Sampietro, G., Santeusanio, G., Santini, D., Silano, M., Solina, G., Tonelli, F., Trapani, D., Usai, P. |
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| Přispěvatelé: | Vanoli, Alessandro, Di Sabatino, Antonio, Martino, Michele, Klersy, Catherine, Grillo, Federica, Mescoli, Claudia, Nesi, Gabriella, Volta, Umberto, Fornino, Daniele, Luinetti, Ombretta, Fociani, Paolo, Villanacci, Vincenzo, D'Armiento, Francesco P., Cannizzaro, Renato, Latella, Giovanni, Ciacci, Carolina, Biancone, Livia, Paulli, Marco, Sessa, Fausto, Rugge, Massimo, Fiocca, Roberto, Corazza, Gino R., Solcia, Enrico, D'Armiento, Francesco P, Corazza, Gino R |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Pathology small bowel carcinoma celiac disease immunology gastrointestinal cancer Kaplan-Meier Estimate Histogenesis Biology Small Gastroenterology Pathology and Forensic Medicine NO Surgical pathology immunology inflammatory bowel disease 03 medical and health sciences small bowel carcinoma 0302 clinical medicine Crohn Disease Internal medicine Intestine Small Intestinal Neoplasms medicine Carcinoma Humans 2734 small bowel carcinoma coeliac disease Crohn's disease Proportional Hazards Models Retrospective Studies Crohn's disease Settore MED/12 - Gastroenterologia Celiac Disease Female Middle Aged Microsatellite instability Anatomical pathology medicine.disease digestive system diseases Intestine 030104 developmental biology Dysplasia 030220 oncology & carcinogenesis Hematopathology celiac disease |
| Popis: | Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (beta-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage-and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear beta-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat beta-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and/or pancreatobiliary-type) mucosa, often through dysplastic polypoid growths of metaplastic phenotype. In conclusion, despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn's disease-associated small bowel carcinomas differ substantially in histological structure, phenotype, microsatellite instability/tumor-infiltrating lymphocyte status, Wnt pathway activation, mucosal precursor lesions and prognosis. |
| Databáze: | OpenAIRE |
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