gms | German Medical Science

Objective: To clarify whether Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and inducible Nitric Oxide Synthase (iNOS) are involved in the angiogenesis and recurrence of spinal chordoma tissues and influence the overall survival. Furthermore to investigate the expression of platelet-derived growth factor (PDGF) receptor A (PDGFRα), epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition factor (c-Met) in spinal chordoma. To the authors’ knowledge, little is known regarding the significance of receptor tyrosine kinase in spinal chordoma related to prognostic value.

Method: All patients affected by a spinal chordoma surgically treated between 1986 and 2007 were reviewed. We examined the expression of VEGFR2 and iNOS with immunohistochemistry using a tissue microarray containing 120 chordoma samples. Local recurrence and overall survival were analyzed. The authors investigated furthermore PDGFR-α, EGFR and c-MET expression in 52 primary and 104 recurrent lesions, and compared it with clinicopathologic Parameters.

Results: A series of 40 operated chordoma patients for a total of 120 lesions (including 80 recurrent lesions) were identified (sacrum 77.5%, lumbar spine 17.5%, cervical/thoracic spine 5%). Surgical margins were wide in 30 (75%), marginal in 8 (20%) and intralesional in 2 (5%) patients. Median follow-up was 120 months. The 5- and 10-year overall survival of the entire series were 78.6% and 30%, respectively. There were 5 primary chordoma (12.5%) with moderate and 35 (87.5%) with strong expression of VEGFR-2. All recurrent spinal chordomas displayed strong expression of VEGFR-2. The expression of iNOS was predominately moderate to high in primary chordomas: There were 15 tumors (37.5%) with moderate and 25 tumors (62.5%) with strong expression. All recurrent chordomas displayed strong expression of iNOS. PDGFR-α, EGFR and c-MET were found to be expressed in 75.0%, 83%, 77% of primary and 97.0% of recurrent lesions. Higher PDGFR-α and c-MET expression was found to be correlated with younger patient age. Lesions with a higher expression of PDGFR-α demonstrated significantly higher EGFR score in both primary and recurrent lesions compared with those with lower PDGFR-α expression. In recurrent lesions, higher c-MET expression was found to be associated with significantly better prognosis than those with lower c-MET expression (p=0.013). Lesions with a higher level of PDGFR-α expression were found to have a significantly poorer prognosis than those with lower PDGFR-α expression (p=0.024).Those patients with lower EGFR expression were found to have a significantly better prognosis than those with higher EGFR expression (p= 0.007).

Conclusions: The high expression of VEGFR-2 and iNOS affected the overall survival. The overall survival at 10 years was only 30%. The c-MET expression was found to be correlated with a younger patient age, and a favorable prognosis in patients with spinal chordoma. Patients with a higher level of PDGFR-α and EGFR expression were found to have a significantly poorer prognosis than those with lower PDGFR-α and EGFR expression.