• Youssef Yakkioui, Yasin Temel, David Creytens, Ali Jahanshahi, Ruth Fleischeuer, René G C Santegoeds, and Jacobus J Van Overbeeke.
• Department of Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands; European Graduate School of Neuroscience, Maastricht, The Netherlands; School for Oncology and Developmental Biology, Maastricht, The Netherlands.
• World Neurosurg. 2014 Jul 1;82(1-2):e311-8.

ObjectiveDespite refinement of surgical techniques and adjuvant radiotherapy, the prognosis for patients with a chordoma remains poor. Identification of prognostic factors related to tumor biology might improve this assessment and result in molecular markers for targeted therapy. Limited studies have been performed to unravel the impact of cell-cycle markers in chordoma, and those performed have shown inconclusive results. In the current study, we aimed to discover the impact of cyclin-dependent kinase 4 (CDK4) expression and its relation to prognosis and other cell-cycle markers in chordoma.MethodsTwenty-five human formalin-fixed, paraffin-embedded chordoma specimens were examined by immunohistochemistry for the expression of CDK4, protein 53 (p53), and murine double minute 2 (MDM2). The MIB-1 labeling index and mitotic index were used for the examination of proliferation. We collected detailed demographic and clinical data.ResultsOverexpression of CDK4, p53, and MDM2 was found in five (20%), seven (28%), and 14 (56%) of the cases, respectively. All three cell-cycle markers showed a significant correlation with MIB1 labeling index. Expression of CDK4 (P = 0.02) and p53 (P < 0.01) were both significantly correlated with poor overall survival. Also, histologically observed necrosis (P < 0.05) and a dedifferentiated tumor subtype (P < 0.01) were related to adverse patient outcome.ConclusionOur results show that the expression of CDK4 and p53 are related to cell proliferation capacity and worse outcome in patients with chordoma.Copyright © 2014 Elsevier Inc. All rights reserved.

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