Clinicopathological Features and Gene Mutation Analysis of Gastrointestinal Stromal Tumors: A Series of 58 Patients

【Background】In gastrointestinal stromal tumors (GISTs), mutually exclusive gain-of-function mutations of KIT and PDGFRA are associated with different mutation-dependent clinical behavior. The study aims to analyze the characteristics of the clinicopathology and genotypes in GISTs in China.【Methods】All adult patients with GIST located in the stomach or small intestine who underwent surgical resections in the Cancer Hospital, Chinese Academy of Medical Sciences from January 2009 to January 2019 without prior Imatinib(Glivec) treatment were included. Specimens were collected for histopathological examination, and mutations in c-kit and PDGFRα genes were analyzed by PCR and the next generation sequencing(NGS). The clinicopathological characteristics of each gene were also analyzed.【Results】A total of 58 GIST patients was included in the study. Among the genotypes, there were 51(87.9%) c-kit mutations, five(8.6%) PDGFRα mutations, and two(3.4%) wild-type mutations. Among the cell types, there were 40 cases(69.0%) of spindle cell type, three cases(5.2%) of epithelioid cell type, and three cases(5.2%) of mixed cell type. Among the four mutant forms of c-kit exon-11, the most common were point mutation in 16 cases(38.1%), deletion mutation in 13 cases(31.0%), insertion mutation in four cases(9.5%), and mixed mutation in nine cases(21.4%). According to the National Institutes of Health(NIH) risk grade, there were three cases(5.2%) with very-low risk, nine cases(15.5%) with low risk, 19 cases(32.8%) with medium risk, and 23 cases(39.7%) with high risk. There were significant differences in cell types among different gene types(P = 0.022) and significant differences in tumor risk among different mutant forms of c-kit gene exon-11(P = 0.039).【Conclusion】In c-kit mutations, spindle cell type was significantly more than epithelioid cell type and mixed cell type. In PDGFRα mutations, spindle cell type and mixed cell type were prevalent. In wild type, spindle cell type and epithelioid cell type were significantly common. A high risk of deletion mutation and mixed mutation is expected in the c-kit exon-11 mutation form, while the intermediate risk of point and insertion mutations are common.