Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer

The main cause of prostate cancer- related mortality is the development of hormone- refractory disease. Circulating serum levels of IL-6 are raised in hormone- refractory prostate cancer patients and evidence from cell line studies suggests that the IL- 6R/ JAK/ STAT3 pathway may be involved in development of this disease. In the current study we investigate if expression levels of these family members are implicated in the development of hormone- refractory prostate cancer. Immunohistochemistry using IL- 6R, JAK1, STAT3, pSTAT3(Tyr705) and pSTAT3(Ser727) antibodies was performed on 50 matched hormone- sensitive and hormone- refractory tumours pairs. An increase in expression of cytoplasmic IL- 6 receptor, with the development of hormone- refractory prostate cancer was associated with reduced time to relapse ( P= 0.0074) while an increase in expression of cytoplasmic pSTAT3(Tyr705) was associated with reduced patient survival ( P= 0.0003). In addition, those patients with high expression of cytoplasmic pSTAT3(Tyr705) in their hormone- refractory tumours had significantly shorter time to death from biochemical relapse and overall survival in comparison to those patients with low expression of cytoplasmic pSTAT3(Tyr705) ( P= 0.002 and P= 0.0027, respectively). Activation of STAT3, via phosphorylation is associated with reduced patient survival, suggesting that activation of the IL- 6R/ JAK/ STAT3 pathway is involved with development of hormone- refractory prostate cancer.