Gastrointestinal stromal tumors: clinical significance of p53 expression, MDM2 amplification, and KIT mutation status.
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.
ARUP Institute for Clinical and Experimental Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Michelle L
ML
Wallander
Lester J
LJ
Layfield
Sheryl R
SR
Tripp
Robert L
RL
Schmidt
D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D019009:Proto-Oncogene Proteins c-kit