Expression of tSTAT3, pSTAT3 727 , and pSTAT3 705 in the epithelial cells of hormone-naïve prostate cancer.

Background The signal transducer and activator of transcription 3 (STAT3) pathway is observed to be constitutively activated in several malignancies including prostate cancer (PCa). In the present study, we investigated the expression of total STAT3 (tSTAT3) and two forms of activated phosphorylated STAT3 (pSTAT3(727) and pSTAT3(705)) in tissue microarrays (TMA) of two cohorts of localized hormone-naive PCa patients and analyzed associations between the expression and disease outcome. Methods The expression of tSTAT3, pSTAT3(727), and pSTAT3(705) was scored in the nuclei and cytoplasm of prostatic gland epithelial cells in two TMAs of paraffin-embedded prostatic tissue. The TMAs consisted of tissue originated from hormone-naive radical prostatectomy patients from two different sites: Malmo, Sweden (n = 300) and Dublin, Ireland (n = 99). Results The nuclear expression levels of tSTAT3, pSTAT3(727), and pSTAT3(705) in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Cytoplasmic tSTAT3 levels were also higher in benign glands. Patients with low pSTAT3(727) and pSTAT3(705) levels in the cancerous glands showed reduced times to biochemical recurrence, compared with those with higher levels. No significant trends in nuclear nor in cytoplasmic tSTAT3 were observed in relation to biochemical recurrence in the Malmo cohort. Higher cytoplasmic tSTAT3 was associated with reduced time to biochemical recurrence in the Dublin cohort. Adding the tSTAT3 and pSTAT3 expression data to Gleason score or pathological T stage did not improve their prognostic values. Conclusions Low pSTAT3(727) and pSTAT3(705) expression in epithelial cells of cancerous prostatic glands in hormone-naive PCa was associated with faster disease progression. However, pSTAT3 and tSTAT3 expression did not improve the prognostic value of Gleason score or pathological T stage and may not be a good biomarker in the early hormone naive stages of PCa.