Small-bowel carcinomas associated with celiac disease: transcriptomic profiling shows predominance of microsatellite instability-immune and mesenchymal subtypes

Rizzo, Francesca; Vanoli, Alessandro; Sahnane, Nora; Cerutti, Roberta; Trapani, Davide; Rinaldi, Antonio; Sellitto, Assunta; Ciacci, Carolina; Volta, Umberto; Villanacci, Vincenzo; Calabrò, Antonio; Arpa, Giovanni; Luinetti, Ombretta; Paulli, Marco; Solcia, Enrico; Sabatino, Antonio Di; Sessa, Fausto; Weisz, Alessandro; Furlan, Daniela

doi:10.1007/s00428-019-02675-w

Cited by 17 publications

(12 citation statements)

References 41 publications

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“…In accordance with previous studies [21][22][23], diffuse, mixed and a few solid-infiltrative cancers with cell clusters protruding from invasive edges, were classified as non-cohesive. Glandular cancers, solid cancers with no glands and luminal space, but retaining some cell polarity and basal membrane differentiation (trabecular pattern), and medullary carcinomas (characterized by expansive growth and abundant infiltration of T lymphocytes due to MSI status or Epstein-Barr virus aetiology [24]), were classified as cohesive.…”

Section: Histology and Immunohistochemistrysupporting

confidence: 83%

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

et al. 2021

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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.

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Section: Histology and Immunohistochemistrysupporting

confidence: 83%

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

et al. 2021

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“…Indeed MSI, which is a consequence of defective DNA mismatch repair, is found at a higher prevalence rate in CeD-SBC (65–73%) compared to CrD-SBC (0–16%) and sporadic SBC (9–35%) [ 171 , 172 , 173 , 179 , 180 , 181 , 182 , 183 ]. Recently, two main subtypes of CeD-SBC have been described, the first with MSI and high TILs, and the second showing prominent TGF-β activation [ 184 ].…”

Section: Celiac Disease and Small Bowel Carcinomamentioning

confidence: 99%

The Risk of Malignancies in Celiac Disease—A Literature Review

Pelizzaro

Marsilio

Fassan

et al. 2021

Cancers

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Celiac disease (CeD) is an immune-mediated enteropathy precipitated by ingestion of gluten in genetically predisposed individuals. Considering that CeD affects approximately 1% of the Western population, it may be considered a global health problem. In the large majority of cases, CeD has a benign course, characterized by the complete resolution of symptoms and a normal life expectancy after the beginning of a gluten-free-diet (GFD); however, an increased risk of developing malignancies, such as lymphomas and small bowel carcinoma (SBC), has been reported. In particular, enteropathy-associated T-cell lymphoma (EATL), a peculiar type of T-cell lymphoma, is characteristically associated with CeD. Moreover, the possible association between CeD and several other malignancies has been also investigated in a considerable number of studies. In this paper, we aim to provide a comprehensive review of the current knowledge about the associations between CeD and cancer, focusing in particular on EATL and SBC, two rare but aggressive malignancies.

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“…This has triggered a number of transcriptomic studies in individuals with both conditions. 3 A meta-analysis of gastrointestinal malignancy in individuals with celiac disease (CD) reported 75 cases of small bowel adenocarcinoma in 79,991 individuals with CD from 8 previous studies (Table 1), corresponding to a pooled odds ratio of 14.4 with heterogeneity >90% for the included studies. 4 The heterogeneity is partly due to mixing of incidence and morbidity ratios, the latter also including prevalent cancers in the risk estimates.…”

Section: Risk Of Small Bowel Adenocarcinomas Adenomas and Carcinoidsmentioning

confidence: 99%

Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease

et al. 2020

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Small-bowel carcinomas associated with celiac disease: transcriptomic profiling shows predominance of microsatellite instability-immune and mesenchymal subtypes

Cited by 17 publications

References 41 publications

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

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

The Risk of Malignancies in Celiac Disease—A Literature Review

Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease

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