Angiogenic Immunoprofile of Variably Aggressive Central Giant Cell Lesions

Objectives: Central giant cell lesions (CGCL) of jawbones reportedly respond to anti-angiogenic therapies. We evaluated expression of vascular markers CD31 and VEGF in human CGCL to investigate angiogenic characteristics. Additionally, we investigated relationships between CD31 and VEGF expression and biologic aggressiveness, as defined by specific clinical parameters. Identification of angiogenic immunoprofiles predictive of aggression and responsiveness to angiogenesis inhibitors would prove beneficial.

Methods: Five aggressive and five non-aggressive lesions were selected from previously diagnosed cases of CGCL. Tissues were immunohistochemically stained with anti-CD31(endothelial marker) and anti-VEGF(pro-angiogenic factor). Immunoprofiling included microvessel density determination (MVD) and percentage of lesional cell staining. MVD was assessed by counting microvessels within the lesion associated with vessel lumina in 19 randomly selected fields(x200 magnification). Percentages of positive staining were determined for VEGF-positive cells (endothelial, mononuclear, giant) in an analogous manner in 16 fields. Data were subjected to Student's t-test to correlate marker expression with aggressive subtypes.

Results: Mean MVD determination for aggressive and non-aggressive CGCL was 13.77(range 12.47-14.89) and 7.32(1.82-9.95) microvessels/x200 field respectively. The five densest CD31-positive lesions all demonstrated clinical aggression(p=0.003). Mean total percent of VEGF-positive cells in aggressive and non-aggressive CGCL was 66.4% (range 43.9-93.7%) and 56.9% (26.2-89.6%) respectively. Four of the five most densely positive lesions for VEGF demonstrated aggressive behavior. Although a trend toward increased VEGF expression in aggressive cases was observed, these data were not statistically significant(p=0.24).

Conclusions: CGCL demonstrate phenotypic markers of angiogenesis as evidenced by expression patterns of CD31 and VEGF. These angiogenic characteristics suggest potential susceptibility to anti-angiogenic therapies. Increased density of CD31 and VEGF-positive cells in aggressive lesions suggests these markers may provide prognostic indication of clinical behavior. Future studies with greater power and additional angiogenic markers are necessary to explore the trends observed.

Study supported by a grant from OHSU School of Dentistry, Dean's Office