Small bowel carcinomas in celiac or Crohn’s disease: distinctive histophenotypic, molecular and histogenetic patterns
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 ca...
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Veröffentlicht in: | Modern pathology 2017-10, Vol.30 (10), p.1453-1466 |
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Zusammenfassung: | 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 (
β
-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
β
-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
β
-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. |
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ISSN: | 0893-3952 1530-0285 |
DOI: | 10.1038/modpathol.2017.40 |