1486PD - Gastrointestinal stromal tumors of the stomach with kit exon 9 mutations mostly present with a favorable prognosis

Date 01 October 2012
Event ESMO Congress 2012
Session Sarcoma
Topics GIST
Translational Research
Presenter Eva Wardelmann
Authors E. Wardelmann1, H. Löser1, W. Jeske1, S. Merkelbach-Bruse1, P. Hohenberger2, P. Reichardt3, S. Bauer4, R. Buettner1, S. Huss1, H. Schildhaus1
  • 1Institute Of Pathology, University of Cologne, 50924 - Cologne/DE
  • 2Dept. Of Surgery, Universitätsklinikum Mannheim, 68167 - Mannheim/DE
  • 3Interdisciplinary Oncology, HELIOS Klinikum Bad Saarow, DE-15526 - Bad Saarow/DE
  • 4Department For Internal Medicine, University of Essen, Essen/DE




Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal (GI) tract. Up to 90% of them carry activating mutations in KIT exons 9, 11, 13, or 17 or PDGFRA exons 12, 14 or 18. We were interested whether the aggressiveness in GIST carrying a mutation in KIT exon 9 is influenced by their primary location.


We evaluated more than 2000 cases in our GIST and Sarcoma Registry Cologne/Bonn (GSRCB) for GIST with KIT exon 9 mutation. Sequences were analysed by direct Sanger Sequencing. We evaluated pathomorphological and clinical data for KIT exon 9 mutated GIST in different primary locations.


We could identify 22 gastric, 73 intestinal and 10 rectal GIST carrying a mutation in KIT exon 9. The average tumor diameter in gastric GIST was 4.8 cm (+/- 4.3 cm) whereas small bowel GISTs (n = 62) were measuring 6.6 cm (+/- 3.4 cm) and rectal GISTs (n = 7) 3.9 cm (+/- 2.1 cm). According to the AFIP classification (Miettinen 2006), 16 gastric tumors belonged to the groups of no or low aggressive behavior. Four GISTs were classified as high risk lesions with a mitotic counts of more than 10/50 HPFs and one GIST measuring 11 cm belonged to the moderate risk group. 13 tumors carried the classical 6 base pairs duplication in KIT exon 9 (p.A502_Y503dup). Interestingly, two tumors showed a novel mutation in KIT exon 9 (p.K474_G487del; p.S476I) which have not been described before. In the small intestine, 31 tumors belonged to the high risk, 11 to the moderate and 22 to the low-risk group. In the group of rectal GIST, 6 of 8 cases were high-risk cases.


KIT exon 9 mutations (typically a 6 bp duplication; p.A502_Y503dup) occur preferentially in a non-gastric location of GISTs. In intestinal cases, this mutational subtype frequently is associated with larger tumors and a high mitotic count, implicating an aggressive behavior. In contrast, gastric tumors with KIT exon 9 mutation more often have a low or no malignant potential.


All authors have declared no conflicts of interest.