This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Herrem, C. J. Articles by Storkus, W. J. Search for Related Content PubMed PubMed Citation Articles by Herrem, C. J. Articles by Storkus, W. J.

Expression of EphA2 is Prognostic of Disease-Free Interval and Overall Survival in Surgically Treated Patients with Renal Cell Carcinoma

Departments of ¹ Immunology and ² Surgery, University of Pittsburgh School of Medicine and ³ University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; ⁴ Department of Molecular Therapeutics, Osaka University, Osaka, Japan; Departments of ⁵ Immunology, ⁶ Hematology & Oncology, and ⁷ Anatomic Pathology, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio; and ⁸ MedImmune, Inc., Gaithersburg, Maryland

Requests for reprints: Walter J. Storkus, Department of Surgery, University of Pittsburgh School of Medicine, 1.32e The Hillman Cancer Center, 5117 Center Avenue, Pittsburgh, PA 15213-1863. Phone: 412-623-3240; Fax: 412-623-7709; E-mail:storkuswj{at}msx.upmc.edu.

Whereas normally expressed at sites of cell-to-cell contact in adult epithelial tissues, recent studies have shown that the receptor tyrosine kinase EphA2 is overexpressed in numerous epithelial-type carcinomas, with the greatest level of EphA2 expression observed in metastatic lesions. In the current study, we have assessed EphA2 expression in archived renal cell carcinoma (RCC) tissues as it relates to patient disease course.

Using specific anti-EphA2 monoclonal antibody 208 and immunohistochemistry, we evaluated EphA2 protein expression levels in RCC specimens surgically resected from 34 patients (including 30 conventional clear-cell RCC, 3 papillary, and 1 chromophobic RCC cases) resulting in clinical cures.

Regardless of histopathologic subtype, RCC lesions expressing higher levels of EphA2 tended to be of a higher grade (P < 0.05) and larger (P = 0.093), more-highly-vascularized tumors (P = 0.005). Perhaps most notable, the degree of EphA2 overexpression (versus normal matched autologous kidney tissue) seemed predictive of short-term (<1 year) versus longer-term (1 year) disease-free interval (P < 0.001) and of overall survival (P < 0.001) among the RCC patients evaluated.

These data suggest that EphA2 expression level may serve as a useful prognostic tool in the clinical management of patients who have been successfully treated with surgery, but who are at greater risk for accelerated disease recurrence and who have a poorer prognosis.

Key Words: Renal Cell Carcinoma • EphA2 • Receptor Tyrosine Kinase • Disease-Free Interval • Immunohistochemistry

This article has been cited by other articles:

				J. Wykosky and W. Debinski The EphA2 Receptor and EphrinA1 Ligand in Solid Tumors: Function and Therapeutic Targeting Mol. Cancer Res., December 1, 2008; 6(12): 1795 - 1806. [Abstract] [Full Text] [PDF]

				A. K. Wesa, C. J. Herrem, M. Mandic, J. L. Taylor, C. Vasquez, M. Kawabe, T. Tatsumi, M. S. Leibowitz, J. H. Finke, R. M. Bukowski, et al. Enhancement in Specific CD8+ T Cell Recognition of EphA2+ Tumors In Vitro and In Vivo after Treatment with Ligand Agonists J. Immunol., December 1, 2008; 181(11): 7721 - 7727. [Abstract] [Full Text] [PDF]

				D. Jackson, J. Gooya, S. Mao, K. Kinneer, L. Xu, M. Camara, C. Fazenbaker, R. Fleming, S. Swamynathan, D. Meyer, et al. A Human Antibody-Drug Conjugate Targeting EphA2 Inhibits Tumor Growth In vivo Cancer Res., November 15, 2008; 68(22): 9367 - 9374. [Abstract] [Full Text] [PDF]

				G. Zhang, C.-N. Njauw, J. M. Park, C. Naruse, M. Asano, and H. Tsao EphA2 Is an Essential Mediator of UV Radiation-Induced Apoptosis Cancer Res., March 15, 2008; 68(6): 1691 - 1696. [Abstract] [Full Text] [PDF]

				R Holm, S Knopp, Z Suo, C Trope, and J M Nesland Expression of EphA2 and EphrinA-1 in vulvar carcinomas and its relation to prognosis J. Clin. Pathol., October 1, 2007; 60(10): 1086 - 1091. [Abstract] [Full Text] [PDF]

				S. A. Hammond, R. Lutterbuese, S. Roff, P. Lutterbuese, B. Schlereth, E. Bruckheimer, M. S. Kinch, S. Coats, P. A. Baeuerle, P. Kufer, et al. Selective Targeting and Potent Control of Tumor Growth Using an EphA2/CD3-Bispecific Single-Chain Antibody Construct Cancer Res., April 15, 2007; 67(8): 3927 - 3935. [Abstract] [Full Text] [PDF]

				A. B. Larsen, M. W. Pedersen, M.-T. Stockhausen, M. V. Grandal, B. v. Deurs, and H. S. Poulsen Activation of the EGFR Gene Target EphA2 Inhibits Epidermal Growth Factor-Induced Cancer Cell Motility Mol. Cancer Res., March 1, 2007; 5(3): 283 - 293. [Abstract] [Full Text] [PDF]

				M. S. Turner, P. A. Cohen, and O. J. Finn Lack of Effective MUC1 Tumor Antigen-Specific Immunity in MUC1-Transgenic Mice Results from a Th/T Regulatory Cell Imbalance That Can Be Corrected by Adoptive Transfer of Wild-Type Th Cells J. Immunol., March 1, 2007; 178(5): 2787 - 2793. [Abstract] [Full Text] [PDF]

				T. Choueiri, B. Rini, J. Garcia, R. Baz, R. Abou-Jawde, S. Thakkar, P Elson, T. Mekhail, M Zhou, and R. Bukowski Prognostic factors associated with long-term survival in previously untreated metastatic renal cell carcinoma Ann. Onc., February 1, 2007; 18(2): 249 - 255. [Abstract] [Full Text] [PDF]

				F. Liu, P. J. Park, W. Lai, E. Maher, A. Chakravarti, L. Durso, X. Jiang, Y. Yu, A. Brosius, M. Thomas, et al. A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma Cancer Res., November 15, 2006; 66(22): 10815 - 10823. [Abstract] [Full Text] [PDF]