title: Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumors: a meta-analysis.
abstract: BACKGROUND
  The postulated relationship between KIT/PDGFRA mutations and their prognostic value in gastrointestinal stromal tumors (GISTs) has generated intense attention during the past decade, despite the fact that a great deal of studies have been conducted on this subject. To provide a strong quantitative estimate of this postulated relationship, we carried out a meta-analysis which combined, compared, and summarized the results of existing relevant studies.
  
  
  METHODS
  Studies were identified by searching databases and reviewing citations in relevant articles. Of 48 potentially relevant studies, we combined individual patient data from 18 studies which involved 1,487 patients with GISTs, by which we made a comparison between the positive KIT mutation subgroup and the negative KIT mutation subgroup (PDGFRA mutation and wild type). We tabulated and analyzed the patient characteristics from each study, including general information such as age and gender, histopathological parameters, and clinical follow-up outcomes.
  
  
  RESULTS
  KIT mutations, compared with PDGFRA mutations and wild type, showed a marked increased risk not only for tumor size (>5 cm) but also for higher mitotic activity (>5), suggesting that KIT mutations significantly correlated with the National Comprehensive Cancer Network (NCCN) high risk or National Institutes of Health (NIH) high risk (1.74 (95% CI, 1.20 to 2.53) and 2.00 (95% CI, 1.08 to 3.68), respectively). Moreover, higher recurrence and metastasis was observed in GISTs with KIT mutations, revealing its closer correlation with clinical malignant risk (P<0.001 for each, with odds ratio (OR) of 2.06 (95%, 1.37 to 3.11) and 2.77 (95%, 1.64 to 4.67), respectively). High risk or malignant GISTs with KIT mutations had a significantly poorer prognosis, as measured by 3-year overall survival, compared to those with PDGFRA mutations and wild type (0.47 (95% CI, 0.25 to 0.90)).
  
  
  CONCLUSIONS
  KIT mutations, compared with PDGFRA mutations and wild type, represent a poorer prognostic marker in high risk or malignant GISTs.
authors.affiliation: Department of Gastrointestinal Surgery, Su Bei People's Hospital of Jiangsu Province, Yangzhou University, Yangzhou, Jiangsu Province 225001, China. 250537471@qq.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zong
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
mesh_terms: D016022:Case-Control Studies; D003131:Combined Modality Therapy; D046152:Gastrointestinal Stromal Tumors / Q000150:complications / Q000235:genetics* / Q000628:therapy; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000209:etiology; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D015996:Survival Rate
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha