Vessel morphometric parameters-correlation with histologic grade and VEGF expression in oligodendroglioma

The contributions of histologic features including microvascular proliferation to the determination of malignancy in oligodendrogliomas remain uncertain. We have retrospectively performed morphometric assessments in 20 tumors histologically classified as well-differentiated (WHO Grade II, n=8) or anaplastic (WHO Grade III, n=12) oligodendrogliomas (WDO or AO). Quantitative studies utilized image analysis of double immunolabeled vasculature with anti CD34 with VIP chromogen (purple) and proliferating nuclei with anti MIB-1, using DAB (brown). Mean values are reported from five fields for each of twenty cases. The total number of MIB-1 positive tumor nuclei was 10 fold higher in AO vs WDO. The area occupied by vessels was also markedly increased in AO vs WDO, as was the microvessel density. Proliferating endothelial cells i.e. those with MIB-1 positive nuclei in CD34 positive cells were significantly increased (4.6 vs 0.26 positive nuclei per unit tumor area, P=0.001) in AO. While in most areas these changes were evident as typical microvascular proliferation, other areas showed thin walled vessels with increased MIB-1 positivity. VEGF was only assessed morphologically and showed positive staining of vasculature only, in WDO, while AO also showed immunoreactivity of vessels and multiple areas of tumor cells. These findings support a contributory role for vascular proliferation in assessing histologic grade. These findings also suggest that VEGF expression which is confined to blood vessels in lower grade tumors but eventually is expressed by tumor cells in higher grade oligodendrogliomas may be an important factor as the tumor progresses.