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- Title
Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn's disease-associated small bowel carcinoma.
- Authors
Arpa, Giovanni; Vanoli, Alessandro; Grillo, Federica; Fiocca, Roberto; Klersy, Catherine; Furlan, Daniela; Sessa, Fausto; Ardizzone, Sandro; Sampietro, Gianluca; Macciomei, Maria Cristina; Nesi, Gabriella; Tonelli, Francesco; Capella, Carlo; Latella, Giovanni; Ciardi, Antonio; Caronna, Roberto; Lenti, Marco Vincenzo; Ciccocioppo, Rachele; Barresi, Valeria; Malvi, Deborah
- Abstract
Most Crohn's disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies.
- Subjects
SMALL intestine; KERATIN; OVERALL survival; PROGNOSIS; SMALL intestine cancer
- Publication
Virchows Archiv: European Journal of Pathology, 2021, Vol 479, Issue 4, p667
- ISSN
0945-6317
- Publication type
Article
- DOI
10.1007/s00428-021-03109-2