Prostate Cancer Relevant Physiology and Pathophysiology

Alternate Names : Adenocarcinoma of the Prostate

Prostate Cancer Relevant Physiology and Pathophysiology

Male gender and age are the most important risk factors for prostate cancer. Although extraordinarily rare in men under the age of 40, prostate cancer reaches a prevalence of 10% in men during the sixth decade of life and nearly 40% by the ninth decade. However, most prostate cancer is occult; only 1% to 2% of men in the ninth decade of life annually manifest clinical evidence of new prostate cancer. Ambient plasma androgen concentrations appear to correlate with the incidence of prostate cancer. Castrated men, men with chronic liver disease who have elevated levels of plasma estrogen, and men with inborn defects of dihydrotestosterone production have lower or negligible risks of prostate cancer. Plasma testosterone concentrations appear to account in part for racial differences in prostate cancer incidence. Black men have the highest incidence of prostate cancer worldwide, American white men have intermediate risk, and Asianmen the lowest risk; these trends in risk correlate with racial differences in inherent androgen concentrations.

The histopathologic precursor for prostate cancer is prostatic intraepithelial neoplasia (PIN) or carcinoma in situ. Benign prostatic hyperplasia (BPH) is not a risk factor for prostatic malignancy. Benign prostatic hyperplasia occurs most commonly within the prostate transition zone, a superficial and relatively small proportion of the gland near the prostatic urethra. In contrast, PIN and prostate cancer most often arise within the peripheral zone of the gland, the largest component of the gland located near the base of the gland and extending to its apex. More than 95% of prostate cancers are adenocarcinomas originating from the glandular acinae and their proximal ducts; tumors arising from these structures are typically responsive to hormonal therapy. The less common histopathologic types of prostate cancer include small cell cancer, carcinoid tumors, adenoid-cystic cancer, mucinous cancer, and sarcomas, which are not typically sensitive to hormonal therapies.

The most useful clinical-pathologic system for classifying prostate cancer is the Gleason grading system. The surgical pathologist examining the biopsied or resected prostatic adenocarcinoma evaluates the primary or dominant degree of differentiation of the tumor and the secondary or next most common degree of differentiation of the tumor. A score (1 to 5) is applied to each of these areas of tumor, and the scores are added. The sum of the scores provides the most consistent assessment of prognosis, with a higher score correlating with a greater frequency of mortality. More recent work has sought to associate other biologic characteristics of prostate carcinomas with clinical behavior and prognosis. Excess DNA content (ploidy); abnormalities of chromosomes 7, 8, 10, or 12; and expression of oncogenes or mutated tumor suppressor genes are beginning to yield important leads to the understanding of prostate cancer carcinogenesis, prognosis, and tumor biology.