Objective       To analyze the clinicopathological characteristics of high-risk gastrointestinal stromal tumor (GIST) and discuss the probable prognostic factors in GIST with the same malignant risk.       Methods       The expression of CD117

CD34

DOG1

Ki67 and P16 were detected by immunohistochemical assay in the tissue samples from 32 patients with high-risk GISTs admitted in our hospital during January 2008 to December 2010. Mutation of C-kit gene was tested by PCR-direct sequencing. The clinicopathologic

immunohistochemical and mutation results were analyzed. The correlation was analyzed between the clinical outcomes of GISTs and the different genotypes and phenotypes of C-kit.       Results       There were 20 cases of pure spindled phenotype and 12 cases of epithelioid/mixed phenotype. The histomorphology of GISTs was different with various anatomic sites. C-kit mutation was detected in 24 cases (75%)

including loss of codon (557-558) in exon 11 in 9 cases

and mutations in  exon 9 in 3 cases. Among the 21 cases with available follow-up data

there were 17 cases found with C-kit mutation

8 cases of epithelioid/mixed phenotype

and 6 cases died or recurred. The mitosis count and the expression of P16 were significantly greater in the cases of dead/tumor-recurrence patients than the patients with non-progression.       Conclusion       High-risk GISTs are tumor with heterogeneity. Comprehensive evaluation of phenotype and genotype is of great significance for clinical practice for GISTs at the same risk. Overexpression of P16 might be a negative prognostic factor.