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.


METHODS
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.


CONCLUSIONS
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.
Bajpai
Jyoti
J
Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
Sharma
Meharchand
M
Sreenivas
Vishnubhatla
V
Kumar
Rakesh
R
Gamnagatti
Shivanand
S
Khan
Shah Alam
SA
Rastogi
Shishir
S
Malhotra
Arun
A
Bakhshi
Sameer
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D012516:Osteosarcoma / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D012372:ROC Curve; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D055815:Young Adult
D042461:Vascular Endothelial Growth Factor A