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World J Gastroenterol. Mar 28, 2008; 14(12): 1891-1897
Published online Mar 28, 2008. doi: 10.3748/wjg.14.1891
KIT exon 11 codon 557/558 deletion/insertion mutations define a subset of gastrointestinal stromal tumors with malignant potential
Katerina Kontogianni-Katsarou, Euthimios Dimitriadis, Constantina Lariou, Evi Kairi-Vassilatou, Nikolaos Pandis, Agatha Kondi-Paphiti
Katerina Kontogianni-Katsarou, Evi Kairi-Vassilatou, Agatha Kondi-Paphiti, Department of Pathology, Athens Medical School, Areteion University Hospital, Athens, Greece
Constantina Lariou, Department of Pathology, “Evangelismos” General Hospital, Athens, Greece
Euthimios Dimitriadis, Nikolaos Pandis, Department of Genetics, Saint Savvas Anticancer Hospital, Athens, Greece
Author contributions: Kontogianni-Katsarou K and Dimitriadis E contributed equally to this work; Kontogianni-Katsarou K, Dimitriadis E and Kondi-Paphiti A designed research; Kontogianni-Katsarou K, Dimitriadis E performed research and wrote the paper; Lariou C, Kairi-Vassilatou E and Kondi-Paphiti A contributed to histological reports; Pandis N analyzed data.
Correspondence to: Dr. Katerina Kontogianni-Katsarou, Department of Pathology, Areteion University Hospital, Athens, Greece. k.kontogianni@m2k.gr
Telephone: +30-210-7286150
Fax: +30-210-7286150
Received: September 10, 2007
Revised: January 10, 2008
Published online: March 28, 2008

AIM: To study the association of the frequency and pattern of KIT and PDGFRA mutations and clinicopathological factors in a group of patients with gastrointestinal stromal tumors (GIST).

METHODS: Thirty patients with GIST were examined. Exons 9, 11, 13, and 17 of the KIT and exons 12 and 18 of the PDGFRA gene were analyzed for the presence of mutations by PCR amplification and direct sequencing.

RESULTS: KIT or PDGFRA mutations were detected in 21 of the 30 patients (70%). Sixteen patients had mutations within KIT exon 11, three within KIT exon 9, and two within PDGFRA exon 18. GISTs with KIT exon 9 mutations were predominantly located in the small intestine, showed a spindle cell phenotype, and were assessed as potentially malignant. GISTs with KIT exon 11 mutations were located in the stomach and intestine, showed mainly a spindle cell phenotype, and were scored as potentially malignant (P < 0.05). Tumors with KIT exon 11 codon 557/558 deletion/insertion mutations were found to be associated with a potentially malignant clinical behaviour (P < 0.003). GISTs with PDGFRA mutations located in stomach showed a mixed cell phenotype and were classified as of very low or low moderate malignant potential.

CONCLUSION: Determination of KIT and PDGFRA mutations should be additional parameters for the better prediction of GISTs clinical behaviour. Tumors with deletion/insertion mutations affecting codons 557/558 of the KIT gene seem to represent a distinct subset of malignant GISTs.

Keywords: Gastrointestinal stromal tumors, KIT gene, Platelet derived growth factor receptor alpha, Mutations, Malignant