PURPOSE: EphA2 (epithelial cell kinase) is a transmembrane receptor tyrosine kinase that has been implicated in oncogenesis. There are no published data regarding the role of EphA2 in ovarian carcinoma, which is the focus of the present study. EXPERIMENTAL DESIGN: Nontransformed (HIO-180) and ovarian cancer (EG, 222, SKOV3, and A2780-PAR) cell lines were evaluated for EphA2 by Western blot analysis. Five benign ovarian masses, 10 ovarian tumors of low malignant potential, and 79 invasive ovarian carcinomas were also evaluated for EphA2 expression by immunohistochemistry. All samples were scored in a blinded fashion. Univariate and multivariate analyses were used to determine significant associations between EphA2 expression and clinicopathological variables. RESULTS: By Western blot analysis, EG, 222, and SKOV3 cell lines overexpressed EphA2, whereas A2780-PAR and HIO-180 had low to absent EphA2 expression. All of the benign tumors had low or absent EphA2 expression. Among the invasive ovarian carcinomas examined (mean age of patients was 59.2 years), 60 (75.9%) tumors overexpressed EphA2 and the other 19 tumors had negative or minimal EphA2 expression. There was no association of EphA2 overexpression with ascites, likelihood of nodal positivity, pathological subtype, and optimum surgical cytoreduction (residual tumor <1 cm). However, EphA2 overexpression was significantly associated with higher tumor grade (P = 0.02) and advanced stage of disease (P = 0.001). The median survival for patients with tumor EphA2 overexpression was significantly shorter (median, 3.1 years; P = 0.004); the median survival for patients with low or absent EphA2 tumor expression was at least 12 years and has not yet been reached. In multivariate analysis using the Cox proportional hazards model, only volume of residual disease (P < 0.04) and EphA2 overexpression (P < 0.01) were significant and independent predictors of survival. CONCLUSIONS: EphA2 overexpression is predictive of aggressive ovarian cancer behavior and may be an important therapeutic target.
PURPOSE:EphA2 (epithelial cell kinase) is a transmembrane receptor tyrosine kinase that has been implicated in oncogenesis. There are no published data regarding the role of EphA2 in ovarian carcinoma, which is the focus of the present study. EXPERIMENTAL DESIGN: Nontransformed (HIO-180) and ovarian cancer (EG, 222, SKOV3, and A2780-PAR) cell lines were evaluated for EphA2 by Western blot analysis. Five benign ovarian masses, 10 ovarian tumors of low malignant potential, and 79 invasive ovarian carcinomas were also evaluated for EphA2 expression by immunohistochemistry. All samples were scored in a blinded fashion. Univariate and multivariate analyses were used to determine significant associations between EphA2 expression and clinicopathological variables. RESULTS: By Western blot analysis, EG, 222, and SKOV3 cell lines overexpressed EphA2, whereas A2780-PAR and HIO-180 had low to absent EphA2 expression. All of the benign tumors had low or absent EphA2 expression. Among the invasive ovarian carcinomas examined (mean age of patients was 59.2 years), 60 (75.9%) tumors overexpressed EphA2 and the other 19 tumors had negative or minimal EphA2 expression. There was no association of EphA2 overexpression with ascites, likelihood of nodal positivity, pathological subtype, and optimum surgical cytoreduction (residual tumor <1 cm). However, EphA2 overexpression was significantly associated with higher tumor grade (P = 0.02) and advanced stage of disease (P = 0.001). The median survival for patients with tumorEphA2 overexpression was significantly shorter (median, 3.1 years; P = 0.004); the median survival for patients with low or absent EphA2tumor expression was at least 12 years and has not yet been reached. In multivariate analysis using the Cox proportional hazards model, only volume of residual disease (P < 0.04) and EphA2 overexpression (P < 0.01) were significant and independent predictors of survival. CONCLUSIONS:EphA2 overexpression is predictive of aggressive ovarian cancer behavior and may be an important therapeutic target.
Authors: Alexander S Hahn; Johanna K Kaufmann; Effi Wies; Elisabeth Naschberger; Julia Panteleev-Ivlev; Katharina Schmidt; Angela Holzer; Martin Schmidt; Jin Chen; Simone König; Armin Ensser; Jinjong Myoung; Norbert H Brockmeyer; Michael Stürzl; Bernhard Fleckenstein; Frank Neipel Journal: Nat Med Date: 2012-06 Impact factor: 53.440
Authors: Mian M K Shahzad; Yong-Hyun Shin; Koji Matsuo; Chunhua Lu; Masato Nishimura; De-Yo Shen; Yu Kang; Wei Hu; Edna M Mora; Cristian Rodriguez-Aguayo; Arvinder Kapur; Justin Bottsford-Miller; Gabriel Lopez-Berestein; Aleksandar Rajkovic; Anil K Sood Journal: Cancer Lett Date: 2012-07-07 Impact factor: 8.679
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