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
Basic Principles in the Management and Treatment (of cancer)
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.