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 (<or=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 epithelial MMP-9 (P = .02), whereas EphA2 overexpression in tumor cells was significantly associated with high MVD (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.
Lin
Yvonne G
YG
Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Han
Liz Y
LY
Kamat
Aparna A
AA
Merritt
William M
WM
Landen
Charles N
CN
Deavers
Michael T
MT
Fletcher
Mavis S
MS
Urbauer
Diana L
DL
Kinch
Michael S
MS
Sood
Anil K
AK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053511:Matrix Metalloproteinase 14 / Q000032:analysis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D036104:Receptor, EphA2 / Q000032:analysis*
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D036104:Receptor, EphA2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14