High stromal WNT5A is an indicator for low risk prostate cancer

Introduction Prostate cancer (PCa) is the third leading cause of cancer related death in European men. Nearly 90 % of the patients develop bone metastases. Tumor derived WNT5A plays an important role in primary and metastatic PCa. Surrounding stromal cells also produce WNT5A, which determines the biology of PCa, in particular in bone metastases. We previously showed that WNT5A is highly expressed in primary PCa and that high WNT5A expression is associated with a better overall survival. Here we determined the role of stromal WNT5A expression in primary PCa.

Methods A tissue microarray, consisting of 41 benign prostate hyperplasia (BPH) controls and 400 PCa patients, who underwent radical prostatectomy between 1996 and 2005, was immunohistochemically analyzed considering the expression of WNT5A in the tumor surrounding stroma. The cores were scored based on staining intensity as: 0 (no staining), 1 (weak staining), 2 (moderate staining), or 3 (strong staining) and considering the quantity of the stained stromal area: 0 (0 %), 1 (1-25 %), 2 (26-50 %), 3 (51-75 %), or 4 (76-100 %).

Results Expression of stromal WNT5A in BPH and tumor free control samples was 1.1-1.2 fold higher compared to WNT5A expression in tumor surrounding stroma (p < 0.001). Tumor stroma WNT5A expression negatively correlated with the Gleason Score (r2 = 0.02387, p < 0.01). However, overall and disease specific survival was not correlated to tumor stroma WNT5A expression. Stromal WNT5A showed a positive correlation to tumor WNT5A expression (r2 = 0.01793, p < 0.01). Furthermore proliferation (r2 = 0.0382, p < 0.001), and apoptosis (r2 = 0.2771, p < 0.001) of the tumor tissue negatively correlated with stromal WNT5A expression.

Discussion These preliminary data show that high expression of stroma derived WNT5A is an indicator of benign tissue and low risk PCa. As tumor- and stroma-derived Wnt signaling may differently impact on tumor growth, future studies should focus on separately analyzing the Wnt profile of tumor vs. surrounding stromal tissues.

Keywords Prostate Cancer, Bone metastases, Wnt, WNT5A

Korrespondenzadresse Wadim Kisel, Universitätsklinikum Carl Gustav Carus Dresden, UniversitätsCentrum für Orthopädie und Unfallchirurgie, Orthopädie und Unfallchirurgie, Fetscherstr. 74, 01307 Dresden, Deutschland,

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