Article
Specific activity of cyclin dependent kinase 1 as a novel predictor of recurrence risk in stage II colon cancer
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Authors
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Matthias Maak
- Klinikum rechts der Isar, Technische Universität München, Department of Surgery, München
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Eliane Zeestraten
- Leiden University Medical Center, Department of Surgical Oncology, Leiden
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Masaki Shibayama
- Sysmex Corporation, Central Research Laboratories, Kobe
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Tibor Schuster
- Klinikum rechts der Isar, Technische Universität München, Institute for Medical Statistics and Epidemiology, München
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Tomoko Matsushima
- Sysmex Corporation, Central Research Laboratories, Kobe
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Satoshi Nakayama
- Sysmex Corporation, Central Research Laboratories, Kobe
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Helmut Friess
- Klinikum rechts der Isar, Technische Universität München, Department of Surgery, München
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Cornelis J. H. Van De Velde
- Leiden University Medical Center, Department of Surgical Oncology, Leiden
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Hideki Ishihara
- Sysmex Corporation, Central Research Laboratories, Kobe
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Robert Rosenberg
- Klinikum rechts der Isar, Technische Universität München, Department of Surgery, München
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Peter J.K. Kuppen
- Leiden University Medical Center, Department of Surgical Oncology, Leiden
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Klaus-Peter Janssen
- Klinikum rechts der Isar, Technische Universität München, Department of Surgery, München
| Published: | May 20, 2011 |
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Outline
Text
Introduction: Altered cell cycle dynamics and check points are typical features of solid tumors, and cyclin dependent kinases (CDKs) play pivotal roles in these processes. Previously we have demonstrated that CDK-based analysis, composed of CDK1 and CDK2, is a useful prognostic marker for early breast cancer [1], [2]. Clinically, there is a need for risk stratification in patients with stage II colon cancer who have a recurrence risk of 20 to 30 percent. Therefore we investigated the use of CDK-based analysis for recurrence prediction of stage II colon cancer patients who did not receive any adjuvant treatment.
Materials and methods: Fresh frozen tissue samples of 254 patients with colon adenocarcinoma, UICC stage II, who received primary tumor resection in Munich (N=217) and Leiden (N=37) were used.
Protein expression and activity of CDKs were determined by in vitro assays as previously described. Specific activity (SA) was calculated as kinase activity in relation to its corresponding mass concentration.
Results: Development of distant metastasis was observed in 27 patients (10.6%, median follow up=86 months). Predictive performance of CDK1SA, but not CDK2SA, for the metastasis was substantial and almost constant for long-term event prediction (average AUC=0.69). Tumor recurrence risk analysis in association with CDK1SA identified a low- (41% of population) and high-risk group (59%). Cox proportional hazard model analysis retained the CDK-based patient classification as an independent prognostic factor for distant metastases-free survival (low vs. high-risk group: Hazard ratio=6.2, 95% CI: 1.45 to 26.9, p=0.0049). Clinical parameters such as grading, T-categories, age and sex were excluded as confounding factors for CDK1SA-based risk.
Conclusion: CDK1SA allows stratification of different risk subgroups of stage II colon cancer patients. CDK1SA-based analysis is useful for predicting patients with high risk of distant recurrence, who should be treated with chemotherapy.
References
- 1.
- Kim SJ, Nakayama S, Miyoshi Y, Taguchi T, Tamaki Y, Matsushima T, Torikoshi Y, Tanaka S, Yoshida T, Ishihara H, Noguchi S. Determination of the specific activity of CDK1 and CDK2 as a novel prognostic indicator for early breast cancer. Ann Oncol. 2008 Jan;19(1):68-72. DOI: 10.1093/annonc/mdm358
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