Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn’s disease-associated small bowel carcinoma

Giovanni Arpa, Alessandro Vanoli, Federica Grillo, Roberto Fiocca, Catherine Klersy, Daniela Furlan, Fausto Sessa, Sandro Ardizzone, Gianluca Sampietro, Maria Cristina Macciomei, Gabriella Nesi, Francesco Tonelli, Carlo Capella, Giovanni Latella, Antonio Ciardi, Roberto Caronna, Marco Vincenzo Lenti, Rachele Ciccocioppo, Valeria Barresi, Deborah MalviAntonietta D’Errico, Fernando Rizzello, Gilberto Poggioli, Claudia Mescoli, Massimo Rugge, Ombretta Luinetti, Marco Paulli, Antonio Di Sabatino, Enrico Solcia

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalVirchows Archiv
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Cytokeratin 7
  • MUC5AC
  • Non-conventional dysplasia
  • Small bowel adenocarcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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