Linked Life Data

17471475

Source:http://linkedlifedata.com/resource/pubmed/id/17471475

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-6-11
pubmed:abstractText
Approximately 10% of all colorectal carcinomas are mucinous carcinomas, characterized by extracellular mucin. Occasionally, mucin accumulates intracellularly in these tumours, causing signet ring cell differentiation. We hypothesized that signet ring cells arise from a separate genetic pathway. In this study the molecular background of signet ring cell differentiation was investigated by analysing genetic changes, changes in the expression of adhesion molecules, and mucin content. Furthermore, its clinical relevance was addressed. Cell lines of colorectal tumours with non-mucinous (AC), mucinous (MC), and signet ring cell phenotype (MCSRC) were used for Multiplex Ligation-dependent Probe Amplification to detect deletions and amplifications in specific oncogenes and tumour suppressor genes. Furthermore, the expression of E-cadherin, beta-catenin, ITF (intestinal trefoil factor), and MUC2 in signet ring cells was studied by immunohistochemistry, immunofluorescence, and mRNA in situ hybridization. Results were validated using a large cohort of rectal carcinomas from which clinicopathological data were available. Specific amplifications and deletions in cell lines of AC, MC, and MCSRC were detected. Bcl-2 was amplified in MCSRC and MC cell lines, but not in AC cell lines. Bcl-2 FISH analysis confirmed this in patient material. Signet ring cells had decreased expression of adhesion molecules (E-cadherin, beta-catenin) and were strongly positive for ITF and MUC2, two peptides which are normally only produced by goblet cells. RNA in situ hybridization confirmed the production of ITF. Mucinous carcinomas with signet ring cell differentiation presented at a higher T stage than adenocarcinomas and mucinous carcinomas (16% pT4 versus 3-5%, p<0.001) and were more frequently node positive (77% vs 39-44%; p<0.001). Prognosis was significantly worse. In conclusion, the presence of signet ring cells in carcinomas with mucinous differentiation correlates with increased T-stage and poor prognosis. These cells, characterized by ITF and MUC2 production, show disruption of the E-cadherin/beta-catenin complex, as well as amplification of Bcl-2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
212
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
278-86
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17471475-Adenocarcinoma, Mucinous, pubmed-meshheading:17471475-Analysis of Variance, pubmed-meshheading:17471475-Cadherins, pubmed-meshheading:17471475-Carcinoma, Signet Ring Cell, pubmed-meshheading:17471475-Cell Differentiation, pubmed-meshheading:17471475-Cell Line, pubmed-meshheading:17471475-Colorectal Neoplasms, pubmed-meshheading:17471475-DNA Probes, pubmed-meshheading:17471475-Gene Expression, pubmed-meshheading:17471475-Genes, bcl-2, pubmed-meshheading:17471475-Humans, pubmed-meshheading:17471475-Immunohistochemistry, pubmed-meshheading:17471475-In Situ Hybridization, Fluorescence, pubmed-meshheading:17471475-Mucin-2, pubmed-meshheading:17471475-Mucins, pubmed-meshheading:17471475-Neoplasm Staging, pubmed-meshheading:17471475-Peptides, pubmed-meshheading:17471475-RNA, Messenger, pubmed-meshheading:17471475-Statistics, Nonparametric, pubmed-meshheading:17471475-beta Catenin
pubmed:year
2007
pubmed:articleTitle
Signet ring cell differentiation in mucinous colorectal carcinoma.
pubmed:affiliation
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
pubmed:publicationType
Journal Article, Comparative Study, Multicenter Study