Source:http://linkedlifedata.com/resource/pubmed/id/18632876
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2008-11-18
|
| pubmed:abstractText |
The role of Wnt pathway in digestive endocrine tumours is debated. The aim of this work is to investigate key players in Wnt pathway by a multimodal approach. Sixty cases (49 well-differentiated and 11 poorly differentiated) were investigated for methylation of adenomatous polyposis coli (APC) and E-cadherin promoters, the loss of heterozygosity (LOH) at APC locus and beta-catenin and E-cadherin expression by immunohistochemistry. Tumours showing altered beta-catenin localization were tested for beta-catenin and APC mutations. APC promoter methylation was restricted to gastroduodenal tumours (21 out of 59, 36%), prevalent in poorly differentiated carcinomas (P=0.042) and correlating with aggressive features (high histology grade, P<0.02; tumour death, P=0.026; high fractional allelic loss, P=0.002, in turn correlating with short survival, P=0.017). LOH at APC locus was found in 14 out of 53 cases (26%, 10 gastroduodenal and 4 colorectal), prevalent in poorly differentiated carcinomas (P=0.002) and correlating with histology grade (P=0.012). beta-catenin abnormal expression was found in 41 out of 54 cases (76%), with nuclear staining correlating with APC alteration (P=0.047) and short survival (P=0.006). APC, but not beta-catenin, gene mutations were found (7 out of 35 tumours), 4 of which in the midgut. E-cadherin promoter methylation was rarely detected (2 out of 52 cases), with cytoplasmic expression in 18 out of 43 cases (42%), not correlating with any clinico-pathological feature. In conclusion, Wnt pathway alterations, as represented by abnormal beta-catenin localization, are common events in digestive endocrine tumours, but only nuclear expression correlates with tumour aggressiveness. Though with different alteration mechanisms according to anatomical site, APC plays a major role in Wnt pathway activation and in determining the high chromosomal instability observed in aggressive endocrine carcinomas.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
1351-0088
|
| pubmed:author |
pubmed-author:AzzoniCinziaC,
pubmed-author:BordiCesareC,
pubmed-author:BottarelliLorenaL,
pubmed-author:CamisaRobertaR,
pubmed-author:CampaniniNicolettaN,
pubmed-author:D'AddaTizianaT,
pubmed-author:Delle FaveGianfrancoG,
pubmed-author:FellegaraGiovanniG,
pubmed-author:LuongTu VinhTV,
pubmed-author:PasqualiClaudioC,
pubmed-author:PizziSilviaS,
pubmed-author:RindiGuidoG,
pubmed-author:RossiGiulioG,
pubmed-author:TamburiniElisaE
|
| pubmed:issnType |
Print
|
| pubmed:volume |
15
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1013-24
|
| pubmed:dateRevised |
2009-12-1
|
| pubmed:meshHeading |
pubmed-meshheading:18632876-Adenomatous Polyposis Coli Protein,
pubmed-meshheading:18632876-Adult,
pubmed-meshheading:18632876-Aged,
pubmed-meshheading:18632876-Aged, 80 and over,
pubmed-meshheading:18632876-Cell Nucleus,
pubmed-meshheading:18632876-Chromosomal Instability,
pubmed-meshheading:18632876-Cytoplasm,
pubmed-meshheading:18632876-DNA Methylation,
pubmed-meshheading:18632876-Endocrine Gland Neoplasms,
pubmed-meshheading:18632876-Female,
pubmed-meshheading:18632876-Gastrointestinal Neoplasms,
pubmed-meshheading:18632876-Humans,
pubmed-meshheading:18632876-Immunoenzyme Techniques,
pubmed-meshheading:18632876-Loss of Heterozygosity,
pubmed-meshheading:18632876-Male,
pubmed-meshheading:18632876-Middle Aged,
pubmed-meshheading:18632876-Mutation,
pubmed-meshheading:18632876-Promoter Regions, Genetic,
pubmed-meshheading:18632876-Wnt Proteins,
pubmed-meshheading:18632876-Young Adult,
pubmed-meshheading:18632876-beta Catenin
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Adenomatous polyposis coli alteration in digestive endocrine tumours: correlation with nuclear translocation of beta-catenin and chromosomal instability.
|
| pubmed:affiliation |
Section of Pathological Anatomy, Department of Pathology and Laboratory Medicine, University of Parma, via Gramsci, 14, I-43100 Parma, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|