Expression of Vascular Endothelial Growth Factor correlates with the advance of clinical osteosarcoma

Abstract

Purpose: Osteosarcoma is the most common primary malignancy in orthopaedic surgery. Studies suggest that expression of VEGF and high vascularity within osteosarcoma may correlate with poor prognosis. The purpose of this study was to determine whether there was a correlation of VEGF expression with clinical tumour stage and metastasis.

Methods: This retrospective case series examined 54 cases of osteosarcoma patients who were treated during a ten-year period. Relevant clinical information included age, gender, tumour location, stage, adjuvant therapy, morbidity, mortality, and tumour subtypes. The clinical information was analysed for correlation of VEGF expression and tumour prognosis. Tumour sections were examined by routine H&E and by immunohistochemistry for VEGF, CD31, and the oncogenes c-myc and c-fos.

Results: There was a significantly positive correlation between VEGF expression and tumour stages among these cases (p < 0.01). The data also suggested a higher cancer recurrence and more frequent cases of remote metastasis in the high-VEGF group compared to the low-VEGF group. VEGF expression also positively associated with c-fos and c-myc expressions in the primary tumour sections.

Conclusion: The results of this study highlight the role of VEGF in angiogenesis and tumour burden. Data also suggest the influence of VEGF may associate with the elevations of c-fos and c-myc expression. The development of novel therapies to target the VEGF pathway in osteosarcoma may lead to improved survival.

Figures

Fig. 1

Immunohistochemical stains against vascular endothelial growth factor (VEGF) on primary osteosarcoma sections. a Grade 1 (<20 % positive cells). b Grade 2 (<50 % positive cells). c Grade 3 (>50 % positive cells). d Grade 4 (100 % positive). All sections were under 100× magnification

Fig. 2

Regression plot indicates the significant positive correlation of c-fos expression with the increased expression of vascular endothelial growth factor (VEGF) (p < 0.01)

Fig. 3

Vascular endothelial growth factor (VEGF) expression correlates with tumour stages . Tumour stages are converted to numerical numbers for statistical analysis purpose: stage II-A converts to 2.1, III-A to 3.1; where stage II-B converts to 2.5, III-B to 3.5, etc. Though VEGF expression at each level correlates with multiple stages of osteosarcoma, linear regression analysis overall does show a positive correlation between stage of osteosarcoma and VEGF expression (p < 0.01)