Different types of mutations in GISTs: Different clinical implications?

Abstract

20505 Background: Mutations of KIT or PDGFRa are associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of these mutations is still controversial. Methods: We examined 125 patients diagnosed with GISTs. Genomic DNA was extracted from paraffin-embedded tumor tissues and analysed for the presence of KIT exon 9 and 11 mutations and PDGFRa exon 12 and 18 mutations. DFS (Disease Free Survival) was analysed in 92 radically resected patients. The relation between mutations and clinico-pathological factors was analysed using Fisher's exact test and Kaplan-Meyer analysis. Results: KIT mutations occurred in exon 9 in 15 cases and in exon 11 in 78 cases. PDGFRa mutations have been detected mainly in exon 18 (10 cases) and less frequently in exon 12 (3 cases). Exon 11 mutations were as follows: deletions in 58%, point mutations in 30%, insertions and duplications respectively in 4 and 5 cases. Although type of mutations within exon 11 KIT didn't correlate with DFS, a better trend was evident for duplicated and point mutated GISTs. Exon 9 KIT mutated GISTs were associated with intestinal location and higher grade. There was significant association between PDGFRa mutations, gastric location and lower mitotic index. Moreover, PDGFRa mutated and wild type GISTs seemed to have a better outcome. Conclusions: Point mutations and duplications in exon 11 KIT were associated with a better clinical trend in DFS. Exon 9 KIT mutations significantly correlated with intestinal location and higher mitotic count. PDGFRa mutated GISTs were localized in the stomach and seemed to have a favorable clinical behavior. No significant financial relationships to disclose.