EphA2 is a transmembrane
receptor tyrosine kinase that is overexpressed in many
carcinomas. Specific targeting of EphA2 with
monoclonal antibodies is sufficient to inhibit the growth, migration and invasiveness of aggressive
cancers in animal models. Using immunohistochemical analyses, we measured the expression of EphA2 in prostatic
adenocarcinoma, high-grade
prostatic intraepithelial neoplasia, and adjacent benign prostate tissue from ninety-three radical
prostatectomy specimens. These results were related to multiple clinical and pathologicalcharacteristics. The fraction of cells staining positively with EphA2 in benign prostatic epithelium (mean, 12%) was significantly lower than that in high-grade
prostatic intraepithelial neoplasia (mean, 67%, P < 0.001) and prostatic
adenocarcinoma (mean, 85%, P < 0.001). Moreover, the intensity of EphA2 immunoreactivity in prostatic
adenocarcinoma was significantly higher than in benign prostatic tissue (P < 0.001) or high-grade
prostatic intraepithelial neoplasia (P < 0.001). Benign prostatic epithelium showed weak or no immunoreactivity for EphA2 in all cases examined. Whereas EphA2 immunoreactivity related to neoplastic transformation, it did not correlate with other clinical and pathological parameters examined. Our data suggest that EphA2 levels increase as prostatic epithelial cells progress toward a more aggressive phenotype. Progressively higher levels of EphA2 in high-grade
prostatic intraepithelial neoplasia and prostatic
carcinoma are consistent with recent evidence that EphA2 functions as a powerful oncogene. Moreover, the presence of high levels of EphA2 in these cells suggests opportunities for
prostate cancer prevention and treatment.