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.
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.
Authors: Gulnihal Ozcan; Bulent Ozpolat; Robert L Coleman; Anil K Sood; Gabriel Lopez-Berestein Journal: Adv Drug Deliv Rev Date: 2015-02-07 Impact factor: 15.470
Authors: Michael J Wagner; Rahul Mitra; Mark J McArthur; Wallace Baze; Kirstin Barnhart; Sherry Y Wu; Cristian Rodriguez-Aguayo; Xinna Zhang; Robert L Coleman; Gabriel Lopez-Berestein; Anil K Sood Journal: Mol Cancer Ther Date: 2017-03-06 Impact factor: 6.261
Authors: Masato Nishimura; Eun-Jung Jung; Maitri Y Shah; Chunhua Lu; Riccardo Spizzo; Masayoshi Shimizu; Hee Dong Han; Cristina Ivan; Simona Rossi; Xinna Zhang; Milena S Nicoloso; Sherry Y Wu; Maria Ines Almeida; Justin Bottsford-Miller; Chad V Pecot; Behrouz Zand; Koji Matsuo; Mian M Shahzad; Nicholas B Jennings; Cristian Rodriguez-Aguayo; Gabriel Lopez-Berestein; Anil K Sood; George A Calin Journal: Cancer Discov Date: 2013-09-03 Impact factor: 39.397