Objective: To investigate the correlation of KIT and PDGFRA mutation status with immunohistochemistry (IHC) and clinicopathological features in the primary, recurren tor metastatic gastrointestinal stromal tumors (GIST). Methods: A total of 167 primary GIST including 22 recurrent or metastatic GIST were tested for CD117, DOG1, CD34 and Ki-67 by IHC, and KIT gene exon 9, 11, 13, 17and PDGFRA gene exon12, 18 were analyzed by Sanger sequencing. Results: The frequencies of KIT and PDGFRA mutation in 167 primary GIST were 83.8%(140/167) and 3.0% (5/167), respectively. The mutation frequencies of KIT gene exon 11, exon 9 and exon 17 were 74.9% (125/167),8.4% (14/167) and 0.6% (1/167). Five primary GIST harbored PDGFRA mutations in exon 18,and 4 tumors had D842V mutation. Genetic mutations in KIT gene included point mutations (34.3%,48/140), deletion mutations (40.7%,57/140), duplication mutations (3.6%,5/140), and complicated mutations (deletion-insertion,12.1%,17/140).For GIST with KIT gene exon 11 mutation, Ki-67 index was significantly higher in tumors with non-point mutation than those with point mutations (P=0.0052). In 22 recurrent or metastatic GIST, double-exon mutation on KIT gene were found in 9 cases and 6 case were with mutation in both exon 11 and 17, 2 in exon 11 and 13,and one in exon 9 and 13.In 22 cases with recurrent or metastatic GIST, patients with double KIT exon mutations had a longer median progression-free survival (PFS)(108 months) than those with wild type gene (PFS, 30 months),and single exon mutation (PFS, 60 months)(P=0.0299 and P=0.0111), while no significant difference were observed regarding Ki-67, CD117, DOG1, CD34 expression,tumor size and nuclear mitosis between them. Conclusions: KIT mutations in primary GIST occur more often in exon 11. For primary GIST with KIT exon 11 mutations, Ki-67 index is higher in lesions with non-point mutation than those with point mutation,indicating poor biological beha-vior. In recurrence or metastatic GIST, cases harbor the double KIT exon mutations account for 9/22 and possess a better PFS than those with wild type and singe KIT exon 11 mutation.
