The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer

Abstract

Johny E Elkahwaji1–31Section of Urologic Surgery, 2Section of Medical Oncology and Hematology, 3Genitourinary Oncology Research Laboratory, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Benign prostatic hyperplasia and prostate cancer remain the most prevalent urologic health concerns affecting elderly men in their lifetime. Only 20% of benign prostatic hyperplasia and prostate cancer cases coexist in the same zone of the prostate and require a long time for initiation and progression. While the pathogenesis of both diseases is not fully understood, benign prostatic hyperplasia and prostate cancer are thought to have a multifactorial etiology, their incidence and prevalence are indeed affected by age and hormones, and they are associated with chronic prostatic inflammation. At least 20% of all human malignancies arise in a tissue microenvironment dominated by chronic or recurrent inflammation. In prostate malignancy, chronic inflammation is an extremely common histopathologic finding; its origin remains a subject of debate and may in fact be multifactorial. Emerging insights suggest that prostate epithelium damage potentially inflicted by multiple environmental factors such as infectious agents, dietary carcinogens, and hormones triggers procarcinogenic inflammatory processes and promotes cell transformation and disease development. Also, the coincidence of chronic inflammation and tumorigenesis in the peripheral zone has recently been linked by studies identifying so-called proliferative inflammatory atrophy as a possible precursor of prostatic intraepithelial neoplasia and prostate cancer. This paper will discuss the available evidence suggesting that chronic inflammation may be involved in the development and progression of chronic prostatic disease, although a direct causal role for chronic inflammation or infection in prostatic carcinogenesis has yet to be established in humans. Further basic and clinical research in the area, trying to understand the etiology of prostatic inflammation and its signaling pathway may help to identify new therapeutic targets and novel preventive strategies for reducing the risk of developing benign and malignant tumors of the prostate.Keywords: benign prostatic hyperplasia, prostate cancer, chronic inflammation, inflammatory mediators