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The human prostate gland is located in the pelvis and is surrounded posteriorly by the rectum and superiorly by the bladder. It is a nonessential organ that is suppos­edly involved in maintaining the viability of sperm and in semen production. Due to its compact, walnut-shaped structure, anatomical regions in the prostate are not easily discernible. A concept of anatomical zones which considers the site of origin of different pathologies is used instead. The prostate is then described in terms of a peripheral, a central, and a transition zone as well as an anterior fibromuscular stroma. Benign prostate hyperplasia (BPH) originates mainly in the transition zone, whereas prostate carcinomas commonly arise in the peripheral zone of the prostate.

Histologically, the prostate exhibits a tuboloalveolar gland architecture. An epithelial parenchyma is embedded within a connective tissue matrix, and epithe­lial cells are organized in glands that branch out from the urethra and terminate in secretory acini. In adults, the prostate epithelium is organized as a bilayer consisting of a basal layer of flattened, undifferentiated cells attached to the basement membrane and a layer of terminally differentiated, columnar secretory cells residing on top of the basal cells and facing the gland lumen. This characteris­tic two-layered epithelial architecture develops during puberty under the influence of male sex hormones. Prior to this differentiation process, prostatic ducts and acini are lined with a multilayered epithelium consisting of immature cells.

A third cell type discernible in adult prostate comprises the neuroendocrine cells, which are scattered throughout the basal compartment. They are character­ized by the expression of neuropeptides such as chromogranin and serotonin, and are terminally differentiated androgen-insensitive cells. Luminal cells are char­acterized by expression of the differentiation markers androgen receptor (AR), prostatic acid phosphatase (PAP), and prostate-specific antigen (PSA), which is currently used as a diagnostic marker for early prostate cancer. Basal cells, in contrast, express the antiapoptotic gene bcl-2P^ Both basal and luminal cells also express a characteristic set of cytokeratins, which commonly serve as specific markers of differentiation in epithelial tissues. A further distinction between basal and luminal cells can be made on the basis of growth regulation: Basal cells are androgen-independent, whereas luminal cells are highly dependent on androgens for their growth and survival.

In aging men, the prostate gland usually becomes hyperplastic. This alteration, termed benign prostate hyperplasia (BPH), arises mainly in the transition zone of the prostate. The state is nonmalignant and causes only minor disturbance of well-being. In contrast, prostate intraepithelial neoplasia (PIN), is a premalig-nant lesion that is characterized by a progressive loss of the epithelial two-cell arrangement.

Adenocarcinoma of the prostate accounts for 95% of all cancerous lesions in the prostate. It is the most commonly diagnosed neoplasm after skin cancer and is second only to lung cancer as the leading cause of cancer-related death among men in the Western world. Prostate carcinoma arises primarily in the peripheral zone of the prostate, and its incidence increases dramatically with patient age. Unless detected at an early stage, prostate cancer tends to spread to the pelvic lymph nodes and ultimately localizes at distant lymph nodes or bone. With these sites being hardly amenable to surgery or radiation therapy, treatment of metastatic disease commonly relies on the hormone-responsive nature of the cancer. Like normal prostate, prostate tumors rely on male sex hormones for development and growth. To induce apoptosis in cancer cells, the hypothalamus-pituitary-sex gland signaling axis, which supplies cancer cells with testicular androgen, is inhibited. Such androgen deprivation initially results in a reduction in tumor mass as androgen-dependent cancer cells undergo apoptotic death. Response to hormone therapy is, however, only temporary, and development of androgen-independent disease with tumor progression occurs in virtually all patients 12 to 18 months after the onset of treatment. At this stage, prostate carcinoma is incurable by current treatment strategies, with five-year survival rates as low as 15%.