title: Cyclin-Dependent Kinase Activity Correlates with the Prognosis of Patients Who Have Gastrointestinal Stromal Tumors.
abstract: BACKGROUND
  The estimation of recurrence risk remains a critical issue in relation to gastrointestinal stromal tumors (GISTs) treated with adjuvant therapy. The accuracy of the commonly used risk stratifications is not always adequate.
  
  
  METHODS
  For this study, data were prospectively collected from 68 patients with GISTs who underwent R0 surgery between 2004 and 2009. The results from this analysis cohort were evaluated using the data obtained from an additional 40 patients in the validation cohort. Cyclin-dependent kinase 1 (CDK1)- and CDK2-specific activities were measured using a non-RI kinase assay system.
  
  
  RESULTS
  The specific activities of CDK1 and CDK2, but not their expression, significantly correlated with recurrence. The specific activities of both CDK1 and CDK2 were independently correlated with mitosis and significantly correlated with recurrence-free survival (RFS). In the multivariate analysis, CDK2-specific activity (P = 0.0006), tumor size (P = 0.0347), and KIT deletion mutations (P = 0.0006) were significantly correlated with RFS in the analysis cohort. In the validation cohort, CDK2-specific activity (P = 0.0368) was identified as an independent prognostic factor for tumor recurrences with tumor location (P = 0.0442).
  
  
  CONCLUSIONS
  The results suggest that the specific activities of CDK1 and CDK2 may reflect the proliferative activity of GISTs and that CDK2-specific activity is a good prognostic factor predicting recurrence after macroscopic complete resection of GISTs.
authors.affiliation: Department of Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. tnishida@east.ncc.go.jp.|Department of Surgery, Osaka Police Hospital, Osaka, Japan. tnishida@east.ncc.go.jp.|Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. tnishida@east.ncc.go.jp.
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.affiliation: Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsushima
authors.affiliation: Department of Pathology, Osaka Police Hospital, Osaka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujimoto
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakayama
authors.affiliation: Department of Surgery, Osaka Police Hospital, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Omori
authors.affiliation: Department of Clinical Oncology, Kawasaki Medical School, Kurashiki, Okayama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamura
authors.affiliation: Department of Surgery, Kanagawa Cancer Centre, Yokohama, Kanagawa, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Surgical Pathology, Hyogo College of Medicine, Kobe, Hyogo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.affiliation: Department of Surgery, Osaka Police Hospital, Osaka, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Ueshima
authors.affiliation: Sysmex Corporation, Kobe, Hyogo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology* / Q000556:secondary / Q000601:surgery; D005838:Genotype; D006801:Humans; D007414:Intestinal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D007421:Intestine, Small; D008113:Liver Neoplasms / Q000201:enzymology* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D010534:Peritoneal Neoplasms / Q000201:enzymology* / Q000556:secondary; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012372:ROC Curve; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D012189:Retrospective Studies; D018570:Risk Assessment; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2