| Objective:The aim of this study was to analyze the associations among genotypes,clinicopathological characteristics and the biological behaviors of c-KIT/PDGFRA mutation in patients with gastrointestinal stromal tumors(GIST).Methods:We collected clinical information of 162 patients who underwent genetic testing in the union hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology from July 2014 to July2017.Generally,c-KIT gene exons 9,11,13,17 and exons 12,18 of PDGFRA gene are tested by sanger sequencing.The relationships among c-KIT/PDGFRA mutations,clinicopathological features and biological behaviors were explored.SPSS 22.0software was adopted for data analysis.Pearson chi-square test or Fisher exact probability method was used for analysis of relationships between individual qualitative variables.P<0.05 was interpreted as statistically significant.Results:1 General characteristic1.1 162 cases were available for the study,which included 93(57.4%)males and 69(42.6%)females,and the ratio was 1.3:1.The median age was 54.1 years old(ranging from 21 to 77).Among them,the ?55 years old group was 82(50.6%)and >55 years old was 80(49.4%).1.2 The most common origin of tumor was stomach(n=83,51.2%),followed by small intestine(n=53,32.7%),rectum(n=7,4.3%),and colon(n=1,0.6%).In the rest of the18 cases(11.1%),tumors were located in extragastrointestinal sites,including mesenterium,omentum and retroperitoneum.2 Gene analyses2.1 The c-KIT mutation was predominant(139/162,85.8%)in GIST patients,followed by the wild type(13/162,8.0%),while the PDGFRA mutation was the least(10/162,6.2%).2.2 Deletion mutation was the most frequent pattern of mutation(38.9%,58/149),followed by substitution(26.8%,40/149)and mixed(20.8%,31/ 149).Duplication and insertion were relatively fewer,accounting for 12.1%(18/149),1.3%(2/149),respectively.3 The relationships among gene mutation and clinicopathological features3.1 AgePatients with deletions of ?2 codons in c-KIT had younger age of onset compared with 1 condon deletion(p=0.007,?55 years old).3.2 Tumor location3.2.1 In c-KIT mutant,exon 9 was more likely to be in non-stomach(mainly in small intestine),compared with exon 11(p=0.002).Most substitution in c-KIT 11 mutant were in stomach(p=0.048).3.2.2 There was a relationship between PDGFRA mutant GIST and the primary site of the tumor,and it almost occurred in stomach(p=0.006).3.3 Mitotic index3.3.1 In c-KIT mutant,duplication tended to have higher mitotic index(p=0.034,<5HPF).3.3.2 Patients bearing deletions involving codons 557/558 in c-KIT exon 11 had higher mitotic index than those not involving codons 557/558(p=0.020,>5HPF).3.3.3 Patients with deletions of ?2 codons had higher mitotic index(p=0.002,>5HPF).3.3.4 PDGFRA mutant was related with smaller mitotic index(p=0.022,<5HPF).3.4 ImmunohistochemistryContrary to c-KIT or wild type,PDGFRA mutant GIST had lower positive rates of CD117,CD34 and DOG-1(p<0.05).3.5 Recurrence risk3.5.1 Patients bearing deletions involving codons 557/558 in c-KIT exon 11 had higher recurrence risk(p=0.026).3.5.2 Patients with deletions of ?2 codons had higher recurrence risk(p=0.023).3.5.3 PDGFRA mutant was associated with lower recurrence risk(p=0.001).Conclusion:The present study suggested that c-KIT/PDGFRA mutational status may affect clinicopathological features and biological behaviors of GISTs.Deletion mutations containing codon 557/558 and deletion mutations more than one codons may become new adverse indicators,and the diagnosis of these two mutation types can provide evidence-based medical evidence for the judgment of clinical prognosis. |
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