Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue.

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine that interacts with its receptor in prostate cells, thus regulating proliferative response and differentiation. It also activates the human androgen receptor in prostate cancer cell lines. In order to assess the significance of these findings in vivo, the expression of key elements of the IL-6 signalling pathway, IL-6 and its receptor, was investigated in tissue samples obtained on radical prostatectomy from prostate cancer patients. IL-6 immunohistochemistry was performed on 17 frozen prostate cancer specimens. IL-6 receptor immunostaining was evaluated in 21 paraffin-embedded prostate tumour specimens. In both groups, adjacent areas of high-grade prostatic intraepithelial neoplasia and benign tissue were also investigated. In benign prostatic epithelium, IL-6 was localized predominantly in basal cells, whereas in prostate cancer tissues more IL-6-positive glandular cells were identified. No IL-6 expression was detected in stromal cells on immunohistochemistry, although IL-6 protein was measured in the supernatants obtained from cultured stromal cells by ELISA. IL-6 receptor was expressed in benign prostatic tissue in both epithelial and stromal cells. Furthermore, IL-6 receptor expression was observed in all tumour specimens investigated and the majority of Gleason patterns analysed had more than 50% of cells showing a positive reaction. IL-6 and IL-6 receptor expression patterns in high-grade prostatic intraepithelial neoplasia lesions were similar to those observed in tumour tissues. Taken together, the results of the present study imply that there are paracrine and autocrine IL-6 loops in benign and neoplastic prostate.