Neoexpression of N‐cadherin in E‐cadherin positive colon cancers

Rosivatz, Erika; Becker, Ingrid; Bamba, Masamichi; Schott, Christina; Diebold, Joachim; Mayr, Doris; Höfler, Heinz; Becker, Karl‐Friedrich

doi:10.1002/ijc.20317

Cited by 69 publications

(60 citation statements)

References 58 publications

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“…Thus, a subset of tumors shows de novo expression or up-regulation of N-cadherin concomitant to their invasive stage. This phenomenon has been reported in melanoma (33), breast (20), prostate (24), pancreas (34), colon (35), squamous cell carcinoma (36), but also in bladder (27). Until now, expression of N-cadherin had been observed in a small number of transitional cell carcinoma of the bladder, but no prognostic value had been recognized (27).…”

Section: Discussionmentioning

confidence: 90%

N-Cadherin as a Novel Prognostic Marker of Progression in Superficial Urothelial Tumors

Lascombe

Clairotte

Fauconnet

et al. 2006

Clinical Cancer Research

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Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion and spreading. In bladder cancer, loss or reduced E-cadherin expression has been associated with poor survival, and aberrant expression of N-cadherin has been associated with the invasive phenotype of bladder carcinoma cells. The purpose of this study was to investigate whether N-cadherin expression was associated with the bladder tumor progression. Experimental Design: E-cadherin and N-cadherin expression was evaluated by immunohistochemistry in 101tumors (pT 1 and pT 2 -T 3 ) and by reverse transcription-PCR analysis and immunohistochemistry in 28 other fresh frozen tumors (pT a , pT 1 , and pT 2 -T 3 ). Results: N-cadherin expression was absent in normal urothelium, appeared in stage pT 1 , and increased in pT 2 -pT 3 tumors. In most cases, increased N-cadherin expression in invasive tumors was associated with loss of E-cadherin expression. Progression-free survival and multivariate analyses revealed that N-cadherin expression is an independent prognostic marker for pT 1 tumor progression. Analysis of the 28 frozen tumors by immunohistochemistry and reverse transcription-PCR showed a good correlation between protein and gene expression in pT 1 and pT 2 -T 3 tumors. Interestingly, in pT a tumors, N-cadherin was not immunodetected, whereas mRNA was present in 50% of cases. Conclusion: Regulatory defects in the N-cadherin promoter, abnormalities at the translational, or protein processing levels could explain the discrepancies between protein and mRNA expression. Most importantly, this study identified N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors. Clearly, N-cadherin acts in an invasive mode in bladder cancer, but whether it has a primary role in urothelial neoplastic progression has yet to be investigated.

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Section: Discussionmentioning

confidence: 90%

N-Cadherin as a Novel Prognostic Marker of Progression in Superficial Urothelial Tumors

Lascombe

Clairotte

Fauconnet

et al. 2006

Clinical Cancer Research

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“…Firstly, the sample sizes were relatively small, prohibiting subgroup analyses. Previous studies have shown correlations of increased N-cadherin/reduced E-cadherin expression with advancing stage (Rosivatz et al, 2004) and tumour grade (Bendardaf et al, 2005) in colorectal adenocarcinomas. The former was partly observed in this series, and is being addressed in ongoing studies.…”

Section: Discussionmentioning

confidence: 93%

“…The most striking finding was the presence of specific cadherin and vimentin phenotype. Specifically, normal colonic epithelium is characterised by E-cadherin expression but lack of N-cadherin and vimentin expression; adenocarcinoma is characterised by increased Ncadherin expression in a stepwise manner with advancing stage (Rosivatz et al, 2004), but minimal vimentin expression; and PMP has high expression of N-cadherin and reduced E-cadherin expression. This cadherin phenotype is suggestive of an EMT state, a process important in the progression of neoplasia towards dedifferentiation and more 'malignant' states.…”

Section: Discussionmentioning

confidence: 99%

“…To address the specific feature of excess extracellular mucin production, we determined the differential expression of MUC-2, a mucin with gel-forming physicochemical properties similar to those exhibited by PMP (Kim and Gum, 1995), as well as interleukin-9 (IL-9) and its receptor (IL-9Ra), as IL-9 has been implicated in mucin-producing conditions such as cystic fibrosis (Hauber et al, 2003) and asthma (Louahed et al, 2000). To evaluation the features of PMP dissemination, we determined the expression of molecules involved in cell adhesion and invasion, specifically N-and E-cadherin, and vimentin, as these are important in colorectal (Dorudi et al, 1993;Rosivatz et al, 2004) and other carcinomas (Bringuier et al, 1993;Islam et al, 1996;Hazan et al, 1997;Rubin et al, 2001). In particular, we sought to determine the phenotype of N-cadherin þ /E-cadherinÀ/vimentin þ , as this has been implicated in epithelial -mesenchymal transition (EMT) (Tran et al, 1999), a process important in the progression of neoplasia towards dedifferentiation and more 'malignant' states (Thiery, 2002).…”

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confidence: 99%

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A specific cadherin phenotype may characterise the disseminating yet non-metastatic behaviour of pseudomyxoma peritonei

et al. 2006

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Pseudomyxoma peritonei (PMP) is a rare neoplasm of mainly appendiceal origin, characterised by excess intra-abdominal mucin production leading to high morbidity and mortality. While histological features are frequently indolent, this tumour disseminates aggressively throughout the abdominal cavity, yet seldom metastasises. This study determined the expression of several markers of colorectal differentiation (carcinoembryonic antigen (CEA), cytokeratins (CK20 and CK7), epithelial membrane antigen), mucin production (MUC-2, interleukin-9 (IL-9), IL-9 receptor (IL-9Ra)), and cell adhesion (N-and E-cadherin, vimentin) in PMP tissue (n ¼ 26) compared with expressions in normal colonic mucosa (n ¼ 19) and colorectal adenocarcinoma (n ¼ 26). Expressions of CEA and cytokeratins were similar for PMP as those in colorectal adenocarcinomas with the exception that the CK20À/CK7À pattern was rare in PMP (Fisher's exact test: P ¼ 0.001). Similarly, expressions of mucin-related proteins were comparable for adenocarcinoma and PMP, with the exception that IL-9 expression was uncommon in adenocarcinoma (P ¼ 0.009). Pseudomyxoma peritonei demonstrated a specific pattern of adhesion-related protein expressions of increased N-cadherin, reduced E-cadherin, and increased vimentin (P ¼ 0.004), a phenotype suggesting a possible epithelial -mesenchymal transition state. Primary PMP cell cultures were successfully maintained and demonstrated marker expressions similar to those seen in in vivo tissues. These early characterisation studies demonstrate similarities between PMP and colorectal adenocarcinoma, but also reveal a specific cadherin phenotype that may characterise the distinct non-metastasising behaviour of PMP, and form the basis for future mechanistic and therapy-targeting research.

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“…Moreover, in some of the above-mentioned studies, the precise contribution of stromal and carcinoma cells to the expression of Sna1 was not assessed. May be owing to these reasons, other groups have been unable to detect Snail in some of these tumors (Rosivatz et al, 2004).…”

Section: Discussionmentioning

confidence: 98%