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A comparison of cell-cycle markers in skull base and sacral chordomas

(2014) WORLD NEUROSURGERY. 82(1-2). p.e311-e318
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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. CONCLUSION: Our results show that the expression of CDK4 and p53 are related to cell proliferation capacity and worse outcome in patients with chordoma.
Keywords
Cyclin-dependent kinase 4, Chordoma, MIB-1, Mouse double murine 2, p53, Survival, POTENTIAL THERAPEUTIC TARGETS, TUMOR-SUPPRESSOR, INTRACRANIAL CHORDOMAS, RADIATION-THERAPY, CDK4, P53, EXPRESSION, PROLIFERATION, PROTEIN, OVEREXPRESSION

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MLA
Yakkioui, Youssef et al. “A Comparison of Cell-cycle Markers in Skull Base and Sacral Chordomas.” WORLD NEUROSURGERY 82.1-2 (2014): e311–e318. Print.
APA
Yakkioui, Y., Temel, Y., Creytens, D., Jahanshahi, A., Fleischeuer, R., Santegoeds, R. G., & Van Overbeeke, J. J. (2014). A comparison of cell-cycle markers in skull base and sacral chordomas. WORLD NEUROSURGERY, 82(1-2), e311–e318.
Chicago author-date
Yakkioui, Youssef, Yasin Temel, David Creytens, Ali Jahanshahi, Ruth Fleischeuer, René GC Santegoeds, and Jacobus J Van Overbeeke. 2014. “A Comparison of Cell-cycle Markers in Skull Base and Sacral Chordomas.” World Neurosurgery 82 (1-2): e311–e318.
Chicago author-date (all authors)
Yakkioui, Youssef, Yasin Temel, David Creytens, Ali Jahanshahi, Ruth Fleischeuer, René GC Santegoeds, and Jacobus J Van Overbeeke. 2014. “A Comparison of Cell-cycle Markers in Skull Base and Sacral Chordomas.” World Neurosurgery 82 (1-2): e311–e318.
Vancouver
1.
Yakkioui Y, Temel Y, Creytens D, Jahanshahi A, Fleischeuer R, Santegoeds RG, et al. A comparison of cell-cycle markers in skull base and sacral chordomas. WORLD NEUROSURGERY. 2014;82(1-2):e311–e318.
IEEE
[1]
Y. Yakkioui et al., “A comparison of cell-cycle markers in skull base and sacral chordomas,” WORLD NEUROSURGERY, vol. 82, no. 1–2, pp. e311–e318, 2014.
@article{5935742,
  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. 
CONCLUSION: Our results show that the expression of CDK4 and p53 are related to cell proliferation capacity and worse outcome in patients with chordoma.}},
  author       = {{Yakkioui, Youssef and Temel, Yasin and Creytens, David and Jahanshahi, Ali and Fleischeuer, Ruth and Santegoeds, René GC and Van Overbeeke, Jacobus J}},
  issn         = {{1878-8750}},
  journal      = {{WORLD NEUROSURGERY}},
  keywords     = {{Cyclin-dependent kinase 4,Chordoma,MIB-1,Mouse double murine 2,p53,Survival,POTENTIAL THERAPEUTIC TARGETS,TUMOR-SUPPRESSOR,INTRACRANIAL CHORDOMAS,RADIATION-THERAPY,CDK4,P53,EXPRESSION,PROLIFERATION,PROTEIN,OVEREXPRESSION}},
  language     = {{eng}},
  number       = {{1-2}},
  pages        = {{e311--e318}},
  title        = {{A comparison of cell-cycle markers in skull base and sacral chordomas}},
  url          = {{http://dx.doi.org/10.1016/j.wneu.2013.01.131}},
  volume       = {{82}},
  year         = {{2014}},
}

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