Document Detail


Gastrointestinal stromal tumors: clinical significance of p53 expression, MDM2 amplification, and KIT mutation status.
MedLine Citation:
PMID:  23060298     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Clinical behavior is best predicted by size and mitotic count (risk index). KIT and platelet-derived growth factor receptor α (PDGFRA) mutations have therapeutic and prognostic value but few other prognostically significant molecular markers have been identified. We investigated the prognostic value of p53 protein expression and MDM2 gene amplification in a series of GISTs.
METHODS: Thirty-five GISTs were tested for KIT and PDGFRA mutations, p53 protein expression (high >10% positive by immunohistochemistry) and MDM2 gene amplification (ratio >1.8). Mitotic index (>5/50 HPF), MDM2 amplification status, p53 protein expression, tumor size, and KIT/PDGFRA mutational status were correlated with clinical outcome.
RESULTS: Only a single (3%) GIST was amplified for MDM2. p53 protein expression, mitotic index, and KIT/PDGFRA mutations did not correlate with recurrence or metastasis (P=0.20, 0.50, and 0.08, respectively) but tumor size did (P=0.04). Risk assessment (size and mitotic index) showed a weak association with clinical behavior (P=0.19).
CONCLUSIONS: MDM2 amplification is uncommon in GISTs. Although high p53 expression occurred in 35% of cases, it did not correlate with clinical behavior. Only GIST size predicted clinical outcome.
Authors:
Michelle L Wallander; Lester J Layfield; Sheryl R Tripp; Robert L Schmidt
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Applied immunohistochemistry & molecular morphology : AIMM / official publication of the Society for Applied Immunohistochemistry     Volume:  21     ISSN:  1533-4058     ISO Abbreviation:  Appl. Immunohistochem. Mol. Morphol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-13     Completed Date:  2013-12-30     Revised Date:  2014-03-04    
Medline Journal Info:
Nlm Unique ID:  100888796     Medline TA:  Appl Immunohistochem Mol Morphol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  308-12     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Gastrointestinal Stromal Tumors / diagnosis,  genetics*,  pathology*
Gene Expression Regulation, Neoplastic*
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Mutation*
Proto-Oncogene Proteins c-kit / genetics*,  metabolism
Proto-Oncogene Proteins c-mdm2 / genetics*,  metabolism
Tumor Suppressor Protein p53 / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/Tumor Suppressor Protein p53; EC 2.7.10.1/Proto-Oncogene Proteins c-kit; EC 6.3.2.19/MDM2 protein, human; EC 6.3.2.19/Proto-Oncogene Proteins c-mdm2

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