Chronic prostatic inflammation seems to play a crucial role in the pathogenesis and progression of BPH. The remodeling of prostate tissue caused by an inflammatory injury may promote the structural changes that are commonly associated with benign disease [4]. The stimulus for prostate inflammatory response in old men is considered to be multifactorial; potential causes include hormonal changes, infections (bacterial and viral), autoimmune response, urinary reflux inside the prostate, and systemic inflammation related to metabolic syndrome. Hormonal changes may promote an increased presence of inflammatory infiltrates in the prostate that could be responsible for tissue damage both in epithelial and stromal cells. This event can initiate a chronic process of wound healing which might trigger prostate tissue remodeling and prostatic enlargement. The effect of inflammation on prostate tissue is due to the fact that the prostate is an immunocompetent organ populated by a limited number of inflammatory cells consisting of scattered stromal and intraepithelial T and B lymphocytes, macrophages, and mast cells.

In the adult prostate, a different inflammatory infiltrate pattern has been described according to the inflammation characteristics. The most common infiltrates are CD4+ T lymphocytes, CD19 or CD20 B lymphocytes, and macrophages. Regardless of the trigger, T lymphocytes, macrophages, and B lymphocytes that are [1] present in the adult prostate can generate damage of both epithelial and stromal cells, stimulate cytokine release, and increase the concentration of some growth factors that are able to promote an abnormal remodeling process characterized by fibromuscular growth (Fig. 10.2).

Interleukins and growth factors induce a self-stimulated mechanism characterized by a continuous activation of inflammatory cells, resulting in prostate enlargement. Another leading actor in this pathway is the local hypoxia induced by prostate enlargement itself. As a consequence, reactive oxygen species (ROS) are released and promote neovascularization and further release of growth factors. This mechanism promotes the establishment of a “vicious cycle” that leads to a progressive increase of prostate volume (Figs. 10.3, 10.4, and 10.5).

Prostate cancer (PCa) is the most common cancer in males in Europe. The frequency of incidentally and autopsy-detected cancers is roughly the same in different parts of the world [5]. This finding is in contrast to the incidence of clinical PCa, which differs widely between different geographical areas, being high in the USA and northern Europe. There are some well-established risk factors for PCa: age, ethnic origin, diet, and genetic predisposition. Moreover, the association between prostate inflammation and PCa has already been addressed by various epidemiological studies. Inflammatory cells and ROS produced by immune response mechanisms cause a damage of tissue and genome, as described above. A typical inflammatory infiltrate is usually found in prostate biopsy or in radical prostatectomy specimens. These areas often include prostate cells with a high proliferative index, which is a characteristic aspect of high-grade prostatic intraepithelial neoplasia. As a consequence of this peculiar morphological aspect, these lesions are usually classified as “proliferative inflammatory atrophy” (PIA). PIA is characterized by a very low apoptotic rate, a decreased expression of p27, and hyperproliferation. Morphologically PIA lesions seem to be an intermediate step toward PIN, which is considered as a direct neoplastic precursor. Shah et al. evaluated the distribution of PIA areas in specimens of radical prostatectomy and found that proliferative inflammatory atrophy was significantly more common in the peripheral zone, next to areas of prostatic carcinoma [7]. Moreover these areas seem to present a high nucleic proliferation that is a characteristic aspect of neoplastic degeneration. Concerning the molecular biological aspects, PIA areas usually present an increased expression of glutathione S-transferase P1 (GSTP1) [8]. GSTP1 is involved in the detoxifying process of carcinogens and it is typically overexpressed in inflammatory tissue. A loss of GSTP1 function due to hypermethylation is a common characteristic of prostate cancer cells. Probably a persistent inflammatory state leads to a lack of expression in prostate carcinoma cells. As a consequence, the susceptibility to other genome alterations due to oxidant carcinogens increases and provides a selective growth advantage.