title: A comparison of cell-cycle markers in skull base and sacral chordomas.
abstract: OBJECTIVE
  Despite 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.
  
  
  METHODS
  Twenty-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.
  
  
  RESULTS
  Overexpression 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.
  
  
  CONCLUSIONS
  Our results show that the expression of CDK4 and p53 are related to cell proliferation capacity and worse outcome in patients with chordoma.
authors: 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.
authors: Youssef
authors: Y
authors: Yakkioui
authors: 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. Electronic address: y.temel@maastrichtuniversity.nl.
authors: Yasin
authors: Y
authors: Temel
authors: School for Oncology and Developmental Biology, Maastricht, The Netherlands; Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: David
authors: D
authors: Creytens
authors: 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.
authors: Ali
authors: A
authors: Jahanshahi
authors: Department of Pathology, Sint Elisabeth Hospital, Tilburg, The Netherlands.
authors: Ruth
authors: R
authors: Fleischeuer
authors: Department of Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; European Graduate School of Neuroscience, Maastricht, The Netherlands.
authors: René G C
authors: RG
authors: Santegoeds
authors: 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.
authors: Jacobus J
authors: JJ
authors: Van Overbeeke
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018797:Cell Cycle Proteins / Q000097:blood*; D002817:Chordoma / Q000097:blood* / Q000628:therapy; D016001:Confidence Intervals; D051358:Cyclin-Dependent Kinase 4 / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000097:blood; D012445:Sacrococcygeal Region; D019292:Skull Base Neoplasms / Q000097:blood* / Q000628:therapy; D013125:Spinal Neoplasms / Q000097:blood* / Q000628:therapy; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000097:blood; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D051358:Cyclin-Dependent Kinase 4
keywords: Chordoma; Cyclin-dependent kinase 4; MIB-1; Mouse double murine 2; Survival; p53