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.
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: David S Moura; Rafael Ramos; Antonio Fernandez-Serra; Teresa Serrano; Julia Cruz; Ramiro Alvarez-Alegret; Rosa Ortiz-Duran; Luis Vicioso; Maria Luisa Gomez-Dorronsoro; Xavier Garcia Del Muro; Javier Martinez-Trufero; Jordi Rubio-Casadevall; Isabel Sevilla; Nuria Lainez; Antonio Gutierrez; Cesar Serrano; Maria Lopez-Alvarez; Nadia Hindi; Miguel Taron; José Antonio López-Guerrero; Javier Martin-Broto Journal: Oncotarget Date: 2018-04-03