Cyclin-Dependent Kinase Activity Correlates with the Prognosis of Patients Who Have Gastrointestinal Stromal Tumors

Ann Surg Oncol. 2015 Oct;22(11):3565-73. doi: 10.1245/s10434-015-4438-y. Epub 2015 Feb 24.

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).

Conclusion: 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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CDC2 Protein Kinase / metabolism*
  • Cyclin-Dependent Kinase 2 / metabolism*
  • Disease-Free Survival
  • Female
  • Gastrointestinal Stromal Tumors / enzymology*
  • Gastrointestinal Stromal Tumors / secondary
  • Gastrointestinal Stromal Tumors / surgery
  • Genotype
  • Humans
  • Intestinal Neoplasms / enzymology*
  • Intestinal Neoplasms / pathology
  • Intestinal Neoplasms / surgery
  • Intestine, Small
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Mitosis
  • Peritoneal Neoplasms / enzymology*
  • Peritoneal Neoplasms / secondary
  • Proto-Oncogene Proteins c-kit / genetics
  • ROC Curve
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Retrospective Studies
  • Risk Assessment
  • Sequence Deletion
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Tumor Burden
  • Young Adult

Substances

  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinase 2