Expression of tSTAT3, pSTAT3727 , 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 (pSTAT3727 and pSTAT3705 ) in tissue microarrays (TMA) of two cohorts of localized hormone-naïve PCa patients and analyzed associations between the expression and disease outcome. METHODS: The expression of tSTAT3, pSTAT3727 , and pSTAT3705 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-naïve radical prostatectomy patients from two different sites: Malmö, Sweden (n = 300) and Dublin, Ireland (n = 99). RESULTS: The nuclear expression levels of tSTAT3, pSTAT3727 , and pSTAT3705 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 pSTAT3727 and pSTAT3705 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 Malmö 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 pSTAT3727 and pSTAT3705 expression in epithelial cells of cancerous prostatic glands in hormone-naïve 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 naïve stages of PCa.

Nuclear expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal compartment of localized hormone-naïve prostate cancer.

BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) is involved in the progression of different tumors including prostate cancer (PCa). The expression of STAT3 in benign and malignant epithelium has been described previously but it has not been described in the stromal compartment. The aim of the present study was to evaluate the nuclear expression and prognostic value of different forms of phosphorylated STAT3 in the stromal compartment of non-cancer and cancer areas of prostatic tissue. MATERIAL AND METHODS: Tissue microarray cores from radical prostatectomy of 225 patients with hormone-naïve localized PCa were immunostained for two phosphorylated forms of STAT3, pSTAT3Tyr705 and pSTAT3Ser727. The prognostic value of the expression levels was studied by Cox regression analysis and biochemical recurrence (BCR)-free survival illustrated by Kaplan-Meier curves. RESULTS: Expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal compartment of cancer tissue was lower compared with non-cancer areas. In univariable and multivariable Cox regression analysis, expression levels of pSTAT3Tyr705 and STAT3Ser727 showed similar prognostic value as pathological T-stage, Gleason score and surgical margin status. Kaplan-Meier survival analysis showed that low nuclear expression levels of pSTAT3Tyr705 and pSTAT3Ser727 in stromal cells in cancer compartment and in non-cancer areas were related to BCR-free survival. CONCLUSIONS: Nuclear expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal cells mirrors previous findings in the epithelial component in that it displays prognostic value in men undergoing radical prostatectomy for localized hormone-naïve PCa.