Endocrine Abstracts

INTRODUCTION: Tissue microarrays (TMAs) are a powerful tool to analyze the clinical significance of tens of biomarkers on hundreds of tumors in a parallel fashion. Here, we used TMAs to survey the potential role of different markers as predictors of prognosis or therapy response in prostate cancer.
MATERIAL & METHODS: Two different prostate TMAs were constructed. 1. A prognostic TMA with specimens from 657 patients with clinically localized prostate cancer and longterm follow-up information on progression (median 5.3 years), overall and tumor-specific survival (median 6 years). 2. A progression TMA containing 376 specimens across all stages of progression including 181 untreated localized tumors, 120 hormone-refractory local recurrences and 91 distant metastases. Immunohistochemistry was applied to analyze the expression of the prognostic or predictive markers Ki67, Bcl-2, p53, Syndecan-1, CD10, erbB2, EGFR, Ep-CAM, CD117, MMP2, HSP90 and MUC1.
RESULTS: High Gleason grade, Ki67, and p53 were confimed as markers of adverse prognosis and advanced disease. In addition, Syndecan-1 (CD138), a heparane-sulfate proteoglycane located at the cell surface, predicted early progression and poor survival. Neoadjuvant hormonal therapy was associated with overexpression of Bcl-2 and inhibition of Ki67 LI and CD-10. A significant overexpression in hormone-refractory and metastatic as compared to localized prostate cancer was found for Ki67 (64% vs. 9%), p53 (35% vs. 4%), Syndecan-1 (38% vs. 3%), EGFR (16% vs. 1%), and c-erbB2 (16% vs. 0%). CD117 was not expressed at any stage.
CONCLUSIONS: Tissue microarrays are a powerful tool for the molecular profiling of prostate cancer allowing to rapidly establish clinical correlations of new molecular markers. Syndecan-1 was identified as a new prognostic marker in prostate cancer. P53, Syndecan-1, EGFR and c-erbB2 are preferentially expressed in hormone-refractory and metastatic prostate cancer. Selected inhibition of these targets might offer one strategy to further delay progression of advanced prostate cancer.