title: SKP2 high expression, KIT exon 11 deletions, and gastrointestinal bleeding as predictors of poor prognosis in primary gastrointestinal stromal tumors.
abstract: OBJECTIVE
  Considering the indication of adjuvant therapy, the recurrence risk for primary gastrointestinal stromal tumor (GIST) after surgery needs to be accurately estimated. However, current risk stratification schemes may still have room for improvement. This study seeks to analyze prognostic factors for primary GISTs from 3 aspects, including clinicopathological parameters, immunohistochemical biomarkers, and gene mutational status, and attempts to find novel valuable factors predicting the malignancy potential of GISTs.
  
  
  METHODS
  Retrospective data from 114 primary GIST patients after R0 resection were collected. Clinicopathological data was obtained from medical records and re-evaluated. Immunohistochemical analysis was performed using the Tissue Microarray method for Ki67, p16, p27, p53, SKP2, CD133, and actin. KIT gene exons 9, 11, 13, and 17 and PDGFRα gene exons 12 and 18 were tested for mutations using PCR.
  
  
  RESULTS
  Univariate analysis revealed the following factors as poor prognostic indicators for relapse-free survival with a median follow-up of 50 months: male gender, gastrointestinal bleeding, mitotic index >5/50HPFs, tumor size >5 cm, non-gastric site, necrosis, epithelioid or mixed cell type, surrounding tissue invasion, Ki67>5%, p16>20%, p53 index >10, SKP2>10%, and KIT exon 11 deletion. Besides mitotic index, tumor size and site, SKP2 high expression (RR = 2.91, 95% CI: 1.41-5.99, P = 0.004) and KIT exon 11 deletion (RR = 2.73, 95% CI: 1.04-7.16, P = 0.041) were also independent risk factors in multivariate analysis, with gastrointestinal bleeding also showing a trend towards significance (RR = 1.88, 95% CI: 0.98-3.64, P = 0.059). In addition, gastrointestinal bleeding and SKP2 high expression showed a good ability to stratify high-risk patients further.
  
  
  CONCLUSIONS
  Our results show that gastrointestinal bleeding, SKP2 high expression, and KIT exon 11 deletions may be useful indicators of high recurrence risk for primary GIST patients.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Hepato-Pancreato-Biliary Surgery, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, People's Republic of China.
authors.forename: Ang
authors.initials: A
authors.lastname: Lv
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Li
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Tian
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Guan
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.forename: Chunyi
authors.initials: C
authors.lastname: Hao
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006470:Hemorrhage / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D008940:Mitotic Index; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D012737:Sex Factors
chemical_list: D014408:Biomarkers, Tumor; D044786:S-Phase Kinase-Associated Proteins; D019009:Proto-Oncogene Proteins c-kit