Pathological significance of deletions involving codons 557 and 558 of KIT gene in localized resected gastrointestinal stromal tumors (GIST) of intermediate and high risk: A study by the Spanish Group for Sarcoma Research (GEIS)

Abstract

10051 Background: Approximately 60 to 85% of GISTs harbour activating mutations of the KIT or PDGFRA tyrosine kinase genes. Deletions affecting codons 557–558 of KIT are relevant to prognosis of resected GIST (Martin J, et al. J Clin Oncol. 2005, 23:6190). Methods: GIST of high or intermediate malignant risk according to Fletcher classification (Hum Pathol. 2002;33; 459) with a complete (R0) or microscopic residual (R1) resection were prospectively evaluated. Central pathology review was carried out. The mutational analysis of exons 9, 11, 13 and 17 of KIT and exons 12 and 18 of PDGFRA was undertaken from DNA extracted from paraffin-embedded tissue. The purpose of this study was to explore the correlation between deletion mutation involving 557–558 codons within KIT gene and known prognostic factors in GIST: mitotic count and size. Results: Of the 33 GIST, 19 were gastric, 13 of small bowell and one of other location. Median tumor size was 10.4 cm (1.9–22 cm), and median mitotic count was 2 (1–32). All cases showed an immunostaining with diffuse cytoplasmic pattern of c-kit (CD117). An 82% (27) presented either a KIT (23) or a PDGFRA (4) mutation. Eleven deletions affecting codons 557–558 of KIT were observed. KIT mutations were associated to spindle type histology and PDGFRA mutations to epithelioid histology. No statistical association between tumor size and KIT mutations, including patients with deletions 557–558, was found. Tumors carrying a deletion of codons 557–558 of KIT presented a different median of mitotic count (8 mit × 50 hpf) than the rest (2 mit × 50 hpf), this difference was statistically significant (p = 0,029) in the Mann-Whitney U test. Conclusions: Deletions affecting codons 557–558 of KIT define a group of cases with a high proliferative potential. The prognostic and predictive significance of these findings are waiting for a longer follow-up. No significant financial relationships to disclose.