EphA2 overexpression is associated with angiogenesis in ovarian cancer

BACKGROUND. EphA2 is overexpressed in the majority of ovarian cancers and predicts poor clinical outcome. Based on EphA2's emerging role in angiogenesis, we hypothesized that tumors overexpressing EphA2 demonstrate greater microvessel density (MVD) and matrix metalloproteinase (MMP) expression. METHODS. After institutional Review Board (IRB) approval, 77 invasive epithelial ovarian tumors were analyzed for CD31, EphA2, MMP-2, MMP-9, and MT1-MMP expression. RESULTS. The median age of the patients was 59 years (range, 34-83). EphA2 was overexpressed in 76% of tumors and was associated with advanced-stage disease (P <.001) and high-grade histology (P =.04). MVD was stratified into high (> 12.7 vessels/high-power field [HPF]) versus low (<= 12.7 vessels/HPF) counts. High MVD was significantly associated with advanced stage (P <.001), presence of ascites (P <.001), and suboptimal surgical cytoreduction (P =.01). MMP expression was scored separately in the stromal. (percentage of tumors with high expression: MMP-2 = 43%; MMP-9 74%; MT1-MMP 40%) and epithelial (percentage of tumors with high expression: MMP-2 = 52%; MMP-9 61%; MT1-MMP = 44%) compartments. Endothelial cell EphA2 overexpression correlated with epithelia] MMP-9 (P =.02), whereas EphA2 overexpression in tumor cells was significantly associated with high M-VD (P =.002), as well as strong stromal and epithelial MMP-9 (P =.01 and P =.04, respectively), epithelial MMP-2 (P =.006), and epithelial MT1-MMP (P =.01) expression. CONCLUSIONS. EphA2 overexpression in endothelial and ovarian cancer cells was strongly associated with critical factors involved in angiogenesis and invasion. These findings may explain the poor clinical outcome of patients with EphA2 overexpression.