Analysis of mutation and expression of c-kit and PDGFR-α gene in gastrointestinal stromal tumor

Background/Aims: To investigate the effect of theexpression and mutation of c-kit and PDGFR-alpha gene and its association with clinical pathology and prognosis of gastrointestinal stromal tumor (GIST). Methodology: Paraffin-embedded tissues from 119 GISTs were analyzed for CD 117 and PDGFR-alpha expression by immunohistochemical method. Fifty GISTs were measured for the presence of c-kit exons 9, 11 and 13 mutations and PDGFR-alpha exons 12, 18 mutations. Results: Of 119 GISTs, 104 (87.4%) were positive for CD-117, 65.5% (78/119) were positive for PDGFR-alpha. Positive signals were located mainly on cell membrane and cytoplasma. Overall, c-kit mutations were detected in 42% of GIST patients which were all exon 11 mutations. The types of c-kit exon 11 mutations were heterogeneous and clustered between Codon 556-560, the classic "hot spot" at the 5'end of exon 11. PDGFR-alpha mutations were identified in 20% of all the 50 cases while four of the positive cases did not express detectable CD117. The commonest type of mutation was the point mutation of D842V of exon 18. Mutations of exon 12 were found in 2 GISTs. Conclusions: As a sensitive and specific marker of GIST, PDGFR-alpha can be used in GIST combined with CD117, especially in the diagnosis and differential diagnosis of GIST that does not express CD-117. c-kit oncogenic mutations have no obvious relationship with biological behavior of GIST. PDGFR-alpha oncogenic mutations are more likely seen in giant, CD117-negative GISTs arising outside the gastrointestinal tract and have an unfavorable clinical course. C-kit oncogenic mutations are more likely seen in CD117-positive GISTs arising in the gastrointestinal tract and have no obvious relationship with biological behavior of GISTs. The majority of PDGFR-alpha-mutated GISTs were of epithelioid or mixed cell type while the majority of kit-mutated GISTs were of spindle cell type.