Prostate Massage Guide

Prostate-specific antigen ( PSA ) is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of normal men, and is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer, but this effectiveness has also been questioned.

Rising levels of PSA over time are associated with both localized and metastatic prostate cancer (CaP).

Biochemistry

Prostate-specific antigen (PSA), also known as kallikrein III , seminin , semenogelase , γ-seminoprotein and P-30 antigen ) is a 34 kD glycoprotein manufactured almost exclusively by the prostate gland; PSA is produced for the ejaculate where it liquifies the semen in the seminal coagulum and allows sperm to swim freely. It is also believed to be instrumental in dissolving the cervical mucous cap, allowing the entry of sperm.

It is a serine protease (EC 3.4.21.77) enzyme, the gene of which is located on the nineteenth chromosome (19q13).

Discovery

The discovery of prostate-specific antigen (PSA) is beset with controversy; as PSA is present in prostatic tissue and semen, it was independently discovered and given different names, thus adding to the controversy. Flocks was the first to experiment with antigens in the prostate and 10 years later Ablin reported the presence of precipitation antigens in the prostate. In 1971, Hara characterized a unique protein in the semen fluid, gamma-seminoprotein. Li and Beling, in 1973, isolated a protein, E1, from human semen in an attempt to find a novel method to achieve fertility control. In 1978, Sensabaugh identified semen-specific protein p30, but proved that it was similar to E1 protein, and that prostate was the source. In 1979, Wang purified a tissue-specific antigen from the prostate ('prostate antigen'). PSA was first measured quantitatively in the blood by Papsidero in 1980, and Stamey carried out the initial work on the clinical use of PSA as a marker of prostate cancer.

Serum PSA

PSA is normally present in the blood at very low levels. The reference range of less than 4 ng/mL for the first commercial PSA test, the Hybritech Tandem-R PSA test released in February 1986, was based on a study that found 99% of 472 apparently healthy men had a total PSA level below 4 ng/mL—the upper limit of normal is much less than 4 ng/mL. Increased levels of PSA may suggest the presence of prostate cancer. However, prostate cancer can also be present in the complete absence of an elevated PSA level, in which case the test result would be a false negative. Obesity has been reported to reduce serum PSA levels. Delayed early detection may partially explain worse outcomes in obese men with early prostate cancer.

PSA levels can be also increased by prostate infection, irritation, benign prostatic hyperplasia (BPH), and recent ejaculation, producing a false positive result. Digital rectal examination (DRE) has been shown in several studies to produce an increase in PSA. However, the effect is clinically insignificant, since DRE causes the most substantial increases in patients with PSA levels already elevated over 4.0 ng/mL.

The "normal" reference ranges for prostate-specific antigen increase with age, as do the usual ranges in cancer:

Despite earlier findings, recent research suggests that the rate of increase of PSA (the PSA velocity ) is not a more specific marker for prostate cancer. However, the PSA rate of rise may have value in prostate cancer prognosis. Men with prostate cancer whose PSA level increased by more than 2.0 ng per milliliter during the year before the diagnosis of prostate cancer have a higher risk of death from prostate cancer despite undergoing radical prostatectomy.

Most PSA in the blood is bound to serum proteins. A small amount is not protein bound and is called free PSA . In men with prostate cancer the ratio of free (unbound) PSA to total PSA is decreased. The risk of cancer increases if the free to total ratio is less than 25%. (See graph at right.) The lower the ratio the greater the probability of prostate cancer. Measuring the ratio of free to total PSA appears to be particularly promising for eliminating unnecessary biopsies in men with PSA levels between 4 and 10 ng/mL. However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours.

PSA in other biologic fluids & tissues

It is now clear that the term prostate-specific antigen is a misnomer. It is neither an antigen nor specific to the prostate. Although present in large amounts in prostatic tissue and semen, it has been detected in other body fluids and tissues.

In women, PSA is found in female ejaculate at concentrations roughly equal to that found in male semen. Other than semen and female ejaculate, the greatest concentrations of PSA in biological fluids are detected in breast milk and amniotic fluid. Low concentrations of PSA have been identified in the urethral glands, endometrium, normal breast tissue and salivary gland tissue. PSA also is found in the serum of women with breast, lung, or uterine cancer and in some patients with renal cancer.

Tissue samples can be stained for the presence of PSA in order to determine the origin of malignant cells that have metastasized.

Uses of PSA

Prostate cancer

Screening

Main article: Prostate cancer screening

The U.S. Food and Drug Administration (FDA) has approved the PSA test for annual screening of prostate cancer in men of age 50 and older. PSA levels between 4 and 10 ng/mL (nanograms per milliliter) are considered to be suspicious and should be followed by rectal ultrasound imaging and, if indicated, prostate biopsy. PSA is false positive-prone (7 out of 10 men in this category will still not have prostate cancer) and false negative-prone (2.5 out of 10 men with prostate cancer have no elevation in PSA). Recent reports indicate that refraining from ejaculation 24 hours or more prior to testing will improve test accuracy.

Risk Stratification & Staging

Post-Treatment Monitoring

Each year, up to 70,000 men in the U.S. will have a "biochemical recurrence," a rising PSA level after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based on the individual's risk of progression as well as the likelihood of success and the risks of the treatment.

Forensic identification of semen

PSA was first identified by researchers attempting to find a substance in seminal fluid that would aid in the investigation of rape cases. PSA is now used to indicate the presence of semen in forensic serology. The semen of adult males has PSA levels far in excess of those found in other tissues; therefore, a high level of PSA found in a sample is an indicator that semen may be present. Because PSA is a biomarker that is expressed independently of spermatozoa, it remains useful in identifying semen from vasectomized and azoospermic males.

It is important to note that PSA can also be found at low levels in other body fluids, such as urine and breast milk, thus setting a high minimum threshold of interpretation to rule out false positive results and conclusively state that semen is present. While traditional tests such as crossover electrophoresis have a sufficiently low sensitivity to detect only seminal PSA, newer diagnostics tests developed from clinical prostate cancer screening methods have lowered the threshold of detection down to 4 ng/mL. This level of antigen has been shown to be present in the peripheral blood of males with prostate cancer, and rarely in female urine samples and breast milk. No studies have been performed to assess the PSA levels in the tissues and secretions of pre-pubescent children. Therefore, the presence of PSA from a high sensitivity (4 ng/mL) test cannot conclusively identify the presence of semen, so care must be taken with the interpretation of such results.

Interactions

Prostate-specific antigen has been shown to interact with Protein C inhibitor.

See also

  • False positive/False negative
  • Prostate cancer
  • Prostate cancer screening
  • Tumor markers

References

  1. ^ Andriole GL, Grubb RL, Buys SS, et al. (2009). "Mortality Results from a Randomized Prostate-Cancer Screening Trial". New Eng. J. Med. 360 (13): 1310. doi:10.1056/NEJMoa0810696. PMID 19297565.

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