Frequency of KIT Mutation in Gastrointestinal Stromal Tumors According to Histologic and Immunohistochemical Findings, the First Report from Iran

BACKGROUND: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. They are believed to originate from the interstitial cells of Cajal. Most of these tumors contain activating mutations in the KIT receptor tyrosine kinase. This is the first study in Iran to evaluate GISTs at the molecular level. METHODS: In the present study, during 5 years (2007-2012), we found 50 cases of GISTs (recurrent or treated cases have been omitted) from the affiliated hospitals of Shiraz University of Medical Sciences. Demographic findings and gross characteristics have been extracted from the clinical charts and pathology reports, respectively. In addition, immunohistochemistry for c-KIT and DOG-1 were performed and reviewed by two pathologists. Molecular study for two common exons of KIT (9,11) were performed by PCR and bidirectional DNA sequencing. RESULTS: Among 50 cases of GIST, 17 cases showed wild type KIT and 33 cases (66%) with mutation either in exon 9 or in exon 11. The mutation of exon 9 was detected in 11 (22%) cases, while 29 (58%) cases had mutation of exon 11. In seven cases, both exon 11 and exon 9 mutations were detected at the same time (14%). CONCLUSION: There is significant variation in the frequency of KIT mutation in exon 9 and 11 from the previous reports. Part of this variation in the previous and current studies is due to methodological differences; however, it seems that ethnic differences should not be underestimated. There are very few studies from the geographic region of Iran; however, the reported cases from the countries such as Turkey are very similar to our findings.