Prostate specific antigen (PSA), a member of the human kallikrein gene family, is a serine protease with chymotrypsin-like activity. The mature form of PSA is a single chain glycoprotein of 237 amino acids
containing 7-8% carbohydrate as a single N-linked oligosaccharide side chain. PSA has a molecular weight of approximately 30,000 daltons.
The major site of PSA production is the glandular epithelium of the prostate. PSA has also been found in breast cancers, salivary gland neoplasms, periurethral and anal glands, cells of the male urethra, breast milk, blood and urine. PSA produced in the prostate is secreted into the seminal fluid in high concentrations. A major function of PSA is the proteolytic cleavage of gel-forming proteins in the seminal fluid, resulting in the liquification of the seminal gel and increased sperm mobility.
Low levels of PSA are found in the blood as a result of leakage of PSA from the prostate gland. Increasing levels of serum PSA are associated with prostatic pathology, including prostatitis, benign prostatic hyperplasia (BPH), and cancer of the prostate. PSA occurs in three major forms in blood. The major immunodetectable
form is PSA complexed with the serine protease inhibitor, alpha1-antichymotrypsin (PSA-ACT). Uncomplexed, or free PSA, is the other immunodetectable form of PSA in serum. The majority of free PSA in serum appears to be an inactive form that cannot complex with protease inhibitors and may be either a PSA zymogen or an
enzymatically-inactive, cleaved form of PSA. Equimolar-response PSA assays have an equivalent response to both free PSA and PSA-ACT.
The ARCHITECT Total PSA assay is an equimolar assay. A third form of PSA, a complex with alpha-2-macroglobulin, is not detectable with current immunoassays for PSA due to the engulfment and subsequent
masking of PSA epitopes by the alpha-2-macroglobulin molecule. Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in men in the United States. Early diagnosis of carcinoma of the prostate is hindered by the lack of symptoms in men with localized tumors. Therefore, early detection requires a simple, safe, and inexpensive test for the disease in asymptomatic men. The traditional method for detection of prostate cancer is the digital rectal examination (DRE). However, only 30 to 40% of cancers detected by DRE screening are expected to be confined to the prostate. The frequent finding of locally advanced prostate cancer in screened patients may be due to the inability of DRE to detect tumors of small volume that are most likely to be confined to the prostate. Since patients with small tumors are believed to have the best prognosis, it can be concluded that DRE has limited sensitivity in detecting those tumors with the greatest potential for cure.
In a 1990 publication by Cooner et al., data was presented regarding the clinical use of other diagnostic modalities such as prostate ultrasonography and serum prostate specific antigen for early detection of prostate cancer. This study found that there was a significant increase in predictability for cancer when the DRE and
PSA tests were abnormal. Several other studies have shown that the measurement of serum PSA concentrations offers several advantages in the early detection of prostate cancer. The procedure is more
acceptable to patients, the result is objective and quantitative, and is independent of the examiners skill. In several recent studies of healthy men 50 years or older, serum PSA levels had the greatest ability to predict prostate cancer. These studies concluded that not only is serum PSA measurement a useful addition to rectal examination and ultrasonography in the detection of prostate cancer, but that it is also the most accurate of the three tests for this purpose. In January 1992, the American Urological Association endorsed annual examination with DRE and PSA, for early detection of prostate cancer, beginning at age 50. This was reaffirmed by the American Cancer Society in November 1992. The combined use of DRE and PSA has been shown to result in an increased detection of early stage prostate cancer; however, the benefit of early detection on patient
outcome has not been proven and is the subject of ongoing clinical trials.
PSA testing can have significant value in detecting metastatic or persistent disease in patients following surgical or medical treatment of prostate cancer. Persistent elevation of PSA following treatment, or an increase in a post-treatment PSA level is indicative of recurrent or residual disease. PSA testing is widely accepted as an adjunctive test in the management of prostate cancer patients.
Manufacturer’s Reagent package insert Architect Tatal PSA, September 2017, Abbott Ireland Diagnostics Division, Finisklin Business Park Sligo, Ireland.