The contribution of cell phenotype to the behavior of gastric cancer

Solcia, Enrico; Klersy, Catherine; Vanoli, Alessandro; Grillo, Federica; Manca, Rachele; Tava, Francesca; Luinetti, Ombretta; Fiocca, Roberto

doi:10.1007/s10120-012-0208-8

Cited by 6 publications

(6 citation statements)

References 43 publications

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“…Based on our findings, the MSI hyperimmune subtype, of known better prognostic value among various gastrointestinal cancers, including SBCs, [22][23][24] In both CrD-SBCs and associated mucosa, metaplastic marker expression was commonly associated with loss of canonical intestinal markers, with special reference to the CDX2 transcription factor. This seems interesting as, in keeping with previous findings on gastrointestinal cancers, including SBCs as a whole [17,41,42], we found that CDX2 predicts improved patient survival. Although in the present CrD-SBC series it failed to remain significant at multivariable analysis due to collinearity with stage and histotype, this survival influence of CDX2 expression should be considered in light of the crucial role played by CDX2 in intestinal epithelium differentiation and metaplastic lineage development.…”

Section: Discussionsupporting

confidence: 90%

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: Discussionsupporting

confidence: 90%

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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“…For the assessment of tumor cell phenotype, only cases with at least 10% immunoreactive cells were regarded as positive with the exception of CDX-2, for which a cutoff of 20% was applied. 23 Cases with nuclear accumulation of C-terminal β-catenin in at least 10% of dysplastic/tumor cells was recorded as positive and were also tested for the loss of nuclear expression of N-terminal β-catenin (monoclonal, clone E247, Abcam). Only relatively strong nuclear SOX-9 immunoreactivity, with the same intensity as the deepest intestinal crypt cells, was regarded as positive.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…Results of potential clinico-pathological relevance provided by previous studies are those suggesting a prognostic relevance of tumor cell phenotype, 3,10,11 a selective tumor association with mucosal metaplastic changes 12 or dysplastic lesions [13][14][15] and a pathogenetic role of molecular changes affecting microsatellite instability status, 8,9,16,17 Wnt signaling pathway [18][19][20] or p53 gene involvement. 5 In the present study, we reinvestigated our small bowel carcinoma series aiming to (a) look for any prognostic influence of histopathological structure, with special reference to tumor cell cohesion and stromal desmoplasia, and tumor cell phenotype, according to criteria already developed for the evaluation of gastric cancer; [21][22][23] (b) expand our analysis to Wnt pathway activation signs such as nuclear β-catenin and SOX-9 transcription factor expression, including their correlation with microsatellite instability status; and (c) gain new insights into cancer histogenesis, with special reference to the carcinogenetic process at work in the inflamed non-tumor mucosa of celiac disease-associated or Crohn's diseaseassociated small bowel carcinoma patients.…”

mentioning

confidence: 99%

Small bowel carcinomas in celiac or Crohn's disease: distinctive histophenotypic, molecular and histogenetic patterns

et al. 2017

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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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“…The results indicated that CDX2 overexpression was significantly associated with sex, lower clinical stage, tumor differentiation, lower rate of vascular invasion and lymph node metastasis, as well as higher 5-year survival rate [66] . Several investigators have reported that CDX2 expression is associated with specific morphological and mucin phenotypes of gastric epithelial dysplasia, and decreased progressively with advanced gastric cancer stage, suggesting a possible tumor suppressor role for CDX2 [67][68][69] . However, sample sizes in the meta-analysis were too small, and whether CDX2positive expression is significantly associated with good prognosis in patients with intestinal phenotype gastric cancer remains to be fully investigated in the future.…”

Section: Cancermentioning

confidence: 99%

New insights into the functions and localization of the homeotic geneCDX2in gastric cancer

Yan

Wei

Xie

et al. 2014

WJG

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Gastric cancer is one of the most frequent cancers, and it ranks the third most common cancer in China. The most recently caudal-related homeobox transcription factor 2 (CDX2) is expressed in a large number of human gastrointestinal cancers. In addition, gastric epithelial cell mutations in CDX2 result in tumor promotion, which is characterized by cellular drug resistance and a high proclivity for developing cancer. A series of publications over the past years suggests a mechanism by which CDX2 overexpression results in multidrug resistance. CDX2 appears to forward control regenerating IV and the multidrug resistance 1 expression signaling pathway for regulation of cell drug resistance.

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The contribution of cell phenotype to the behavior of gastric cancer

Cited by 6 publications

References 43 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

Small bowel carcinomas in celiac or Crohn's disease: distinctive histophenotypic, molecular and histogenetic patterns

New insights into the functions and localization of the homeotic geneCDX2in gastric cancer

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