VEGF expression as a prognostic marker in osteosarcoma.

BACKGROUND: The vascular endothelial growth factor (VEGF) pathway is the key regulator of angiogenesis. In osteosarcoma baseline VEGF is of proven prognostic value but prognostic potential of post-NACT VEGF expression is largely unexplored.

PROCEDURE: Treatment naive patients with osteosarcoma were subjected to initial staging workup followed by three cycles of neoadjuvant chemotherapy (NACT) and surgery; resected tumors were assessed for histological necrosis by Huvos grading. Initial biopsy and resected tumor specimens post-NACT were examined for VEGF expression by immunohistochemistry. Positive VEGF expression was considered when intensive positive staining was observed in >10% of the tumor cells. VEGF expression at baseline was compared with grade of tumor; pre-NACT and post-NACT VEGF expression were compared with histological necrosis. Receiver operating characteristic curves were generated to assess best threshold and predictability.

RESULTS: A total of 31 patients were recruited with median age of 17 years (range 5-66 years); male/female ratio was 25:6; 23 patients (74%) were non-metastatic. At baseline, there was 90% concordance between positive VEGF expression and higher histological grade (28/31); baseline VEGF expression did not correlate well with stage and histological necrosis. Twenty-one (67%) were poor and 10 (33%) were good histologic responders; post-NACT VEGF expression as well as VEGF change following NACT significantly correlated with histological necrosis.

CONCLUSION: Positive VEGF expression in surviving tumor cells post-NACT in resected tumors appears to be an important negative prognostic factor in osteosarcoma which may help future therapies to be identified according to the angiogenic potential of the disease.