Abstract C37: Thrombospondin 2 is differentially expressed between prostate cancer and benign prostatic hyperplasia tissues

Introduction: Thrombospondin 2 (TSP2) is a glycoprotein secreted to the extracellular matrix and behaves as an angiogenic and cellular adhesion modulator. Due to its classical role on inhibiting angiogenesis, TSP2 became an interesting target to be studied in prostate cancer (PCa) tumorigenic process. Objectives: The aim of this study was to investigate TSP2 expression profiling in PCa and benign prostate hyperplasia (BPH) in order to characterize its putative application on the differential diagnosis of these prostatic diseases and trying to understand TSP2 roles on PCa progression steps. Methods: TSP2 transcript expression was analyzed by quantitative real time PCR in PCa, BPH and prostate nontumoral samples. The ability of TSP2 transcript expression level to distinguish between PCa and BPH samples was evaluated by receiver operating characteristic (ROC) curve analysis. TSP2 protein expression was assessed by immunohistochemistry analysis on a tissue microarray containing 204 PCa and 66 BPH tumor specimens, using a semi-automated cellular image analysis system. Tissue areas corresponding to tumor epithelia and stromal compartments were manually selected and analyzed independently for TSP2 protein expression by evaluating the percentage of positively stained area and TSP2 staining intensity. Results: TSP2 transcript expression presented a significant downregulated expression pattern in PCa tissues, as compared to BPH samples and prostate non-tumoral samples (p < 0.01). ROC curve analysis of TSP2 transcript expression level can efficiently distinguish PCa from BPH samples and outperformed serum PSA levels to differentiate these two groups of patients (p < 0.01). By using the TMA approach, our data demonstrated that TSP2 is expressed both at the stromal and epithelial compartments of BPH and PCa tissue samples. There were no significant differences in TSP2 mean expression levels between PCa and BPH epithelial compartments. However, we observed a significant downregulation of TSP2 expression at PCa stromal cell compartment, as compared to the corresponding BPH niches (p < 0.05). There were no significant correlation between TSP2 protein expression and several clinical-pathological data from patients included in this cohort. Conclusions: In summary, our data suggest that TSP2 transcript differential expression levels between PCa and BPH samples seems to be an auxiliary tool for PCa diagnosis. Although TSP2 presents a down regulated expression pattern, both at transcript and protein expression levels on PCa samples, it seems that the expression of TSP2 is differentially modulated at the prostate epithelial and stromal cell compartments. These data indicate that the down regulation of TSP2 at the PCa stromal cell compartment could be a positive modulator of PCa progression, as evidenced by the classical roles of TSP2 on inhibiting angiogenesis and activating cell adhesion. Citation Format: Aline Rocha Matos, Claudia M. Coutinho-Camillo, Aline Silva Damascena, Eloisio Alexsandro Silva, Helena Paula Brentani, Francisco P. Fonseca, Fernando Augusto Soares, Etel Rodrigues Pereira Gimba. Thrombospondin 2 is differentially expressed between prostate cancer and benign prostatic hyperplasia tissues [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C37.