Blood Tests

(a) PROSTATE-SPECIFIC ANTIGEN (PSA)

Overview PSA

• Is a 34-kilodalton (kDa) glycoprotein produced by the prostatic secretory epithelial cells which line the acini and the ducts of the prostate gland

• Is expressed in both benign and malignant prostatic conditions

• Is found in high concentrations in semen and is thought to cause liquefaction of the seminal coagulum

• Is elevated in CAP and a variety of benign prostatic diseases (benign prostatic hyperplasia [BPH] and prostatic inflammation)

• Is organ-specific, but serum PSA levels cannot readily differentiate between various prostatic pathologies

• Has a limited specificity and sensitivity for CAP when used in isolation

• Nevertheless, forms the cornerstone of screening for CAP

Normally, the PSA prohormone (proPSA) is secreted into the lumen of the prostatic duct, where it is converted to the active form. A small proportion of the active PSA enters the blood circulation and is found bound to protease inhibitors such as 1-antichymotrypsin and alpha-2-macroglobulin. The remaining active PSA is converted to the inactive PSA form by proteolysis and is found circulating unbound in serum plasma (free PSA). The gene encoding for PSA is located on chromosome 19.

Indications

• Screening tool (in conjunction with digital rectal examination) for the detection of CAP. Annual examinations in men over 50

years of age, or from 40 years of age in high-risk groups (e.g., family history of CAP, African-American)

• Patients suspected of having CAP

• Surveillance and monitoring of CAP patients

Technique

• Patients must be counseled on the nature and implications of PSA testing (i.e., indications, possible need for further investigations such as prostate biopsies, and potential diagnosis of cancer)

• 5 mL of venous blood is required

• Record patient's age

• Age-specific PSA values are derived from commercial immunoassays based on monoclonal antibodies identification

Clinical implications

Normal values

Traditionally, PSA elevation above a cut-off reference value of 4.0 ng/mL has been regarded as abnormal and prostate biopsies are recommended. Since PSA increases with age, a single reference standard would appear inappropriate in men of all ages given that the clinical significance of CAP varies with increasing age. Moreover, though CAP is commoner with advancing age, there is a paradoxical gradual decrease in its clinical significance. Men of all ages do not have the same therapeutic aims. Therefore, attempts to improve the overall specificity and sensitivity, and decrease the number of false negative biopsies have resulted in the increased use of age-specific reference ranges (Table 2.1).

Factors affecting serum PSA

Blood PSA concentration is dependent on patient age, and the increase in PSA with advancing age is attributable to a number of factors including—

• Normal hyperplasia of the aging prostatic epithelial cells

• A higher incidence of subclinical prostatitis

• The growing prevalence of microscopic, but clinically insignificant prostate cancer

• Areas of prostatic infarction

• Increased leakage of PSA into the serum

TABLE 2.1. Age-specific reference ranges

Age range (yr)

PSA (ng/mL)

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