A protease secreted by the epithelial cells of the prostate gland. Serum levels are elevated in patients with benign prostatic hyperplasia and prostate cancer and are used as a screening test for prostate cancer.
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Dictionary:
pros·tate-spe·cif·ic antigen (prŏs'tāt'spĭ-sĭf'ĭk) |
A protease secreted by the epithelial cells of the prostate gland. Serum levels are elevated in patients with benign prostatic hyperplasia and prostate cancer and are used as a screening test for prostate cancer.
| Encyclopedia of Public Health: Prostate-Specific Antigen |
Prostate-specific antigen (PSA) is a 32-kilodalton (kD) serine kinase that functions to liquify the ejaculate. It is technically referred to as "human kallekrin 2." Several conditions such as prostatitis, benign prostatic hyperplasia, prostate cancer, and ejaculation (mild increase) can increase serum PSA levels. Although it has been detected in other tissue, such as the breast, salivary gland, and in other tumors, it is overwhelmingly more specific for the prostate and has more organ specificity than any other existing tumor marker.
Serum PSA is measured in nanogram (ng) quantities and is very sensitive for detecting prostate cancer. After radical surgery, serum measurements should nadir to undetectable levels. The reappearance of measurable PSA is the earliest sign of therapeutic failure. While very low postoperative measurable levels may represent minimal residual benign glands, values of 0.4 ng/ml are almost always associated with disease recurrence. The first approved indication for serum PSA was for the monitoring of patients after radical prostatectomy. Levels between 4.0 and 10.0 ng/ml carry a 16 to 25 percent risk of detecting prostate cancer, while levels above 10.0 ng/ml are associated with a 60 percent risk of prostate cancer.
Although PSA is considered to be the most effective tumor marker in human oncology, its role in screening strategies for prostate cancer has not been completely established. Since its tumor specificity is low, many patients will demonstrate negative findings on a transrectal needle biopsy prompted by an elevated PSA. Earlier concerns, however, that PSA detects clinically insignificant tumors have been dispelled by multiple surgical pathology studies. It has also been repeatedly demonstrated that serum PSA and a digital rectal examination (DRE) detect more prostate cancer than either modality alone, yet prospective randomized data demonstrating a decrease in the prostate cancer deaths due to screening strategies is unavailable. Several prospective trials are in progress, but are several years from maturity. Recent trends in tumor registry data demonstrate a 12 to 16 percent decrease in prostate cancer deaths over the past five years. Most experts agree that there is some role for PSA evaluation in patients, and efforts are underway to establish reasonable guidelines for the use of this marker.
PSA evaluations should generally start at age fifty in most subjects but at age forty in African Americans and those patients with a family history of the disease. The appropriate upper age to abandon screening is problematic, yet recent data suggests that men over the age of sixty-five with an initial PSA value below one have a very small chance of ever developing prostate cancer.
Several attempts have been made to improve the test characteristics of serum PSA. PSA density accounts for the amount of PSA produced proportional to the volume of the prostate gland. A large gland with benign hyperplasia may make more PSA than a smaller gland. A smaller gland with a higher PSA may be suggestive of prostate cancer. An optimal cutoff of 0.15 has been suggested. The volume of the prostate gland cannot be precisely determined with transrectal ultrasound, making practical implementation of this concept difficult.
Age-adjusted PSA (lowering the normal value in patients younger than sixty and raising it in older patients) has been proposed to increase sensitivity in detection in younger patients. In the case of older patients this can lead to more cases of missing significant tumors, however. Some authors suggest lowering the value for young patients and keeping it at 4.0 ng/ml for older patients.
PSA levels tend to increase in men over time. The rate of increase (velocity) may provide some indication of the development of benign or malignant disease. Investigators have noticed that an increase greater than 0.75 ng/year may suggest a significant cancer risk. While this holds up with retrospective evaluations of archival serum samples, it is more difficult to calculate in patients obtaining values over short time intervals or getting evaluated by different assays over time, which may be more variable.
PSA exists as free and complex forms in the blood. Patients with prostate cancer appear to have lower amounts of free PSA in their serum, and those with benign conditions have a higher proportion of their total PSA in the free form. If the percentage of free PSA of the total is greater than 25 percent, the chance for detecting prostate cancer for overall values of 4 to 10 ng/ml is only 5 to 7 percent rather that the usual 16 to 25 percent. Since the determination of a high free-PSA fraction lowers, but does not eliminate, the risk of prostate cancer, it is often used for decisions regarding repeat biopsies rather than the initial evaluation.
(SEE ALSO: Prostate Cancer; Screening; Secondary Prevention)
Bibliography
Carter, H. B.; Pearson, J. D.; Metter, E. J. et al. (1992). "Longitudinal Evaluation of Prostate Specific Antigen Levels in Men with and without Prostate Cancer." Journal of the American Medical Association 267:2215–2217.
Catalona, W. J.; Smith, D. S.; Wolfert, R. L. et al. (1995). "Evaluation of Percentage of Free Serum Prostate-Specific Antigen to Improve Specificity of Prostate Cancer Screening." Journal of the American Medical Association 274:1214–1219.
Morgan, T. O.; Jacobsen, S. J.; McCarthy, W. F. et al. (1996). "Age-Specific Reference Ranges for Serum Prostate-Specific Antigen in Black Men." New England Journal of Medicine 335:304–310.
Oesterling, J. E.; Jacobsen, S. J.; Chute, C. G. et al. (1993). "Serum Prostate-Specific Antigen in a Community-Based Population of Healthy Men. Establishment of Age-Specific Reference Ranges." Journal of the American Medical Association 270:860–864.
Polascik, T. J.; Oesterling, J. E.; and Partin, A. W. (1999). "Prostate Specific Antigen: A Decade of Discovery— What We Have Learned and Where We Are Going." Journal of Urology 162:293–306.
— S. BRUCE MALKOWICZ
| Wikipedia: Prostate specific antigen |
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Kallikrein-related peptidase 3
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| Identifiers | ||||||||||||||
| Symbols | KLK3; APS; KLK2A1; PSA; hK3 | |||||||||||||
| External IDs | OMIM: 176820 MGI: 892021 HomoloGene: 84789 | |||||||||||||
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| RNA expression pattern | ||||||||||||||
| Orthologs | ||||||||||||||
| Human | Mouse | |||||||||||||
| Entrez | 354 | 16617 | ||||||||||||
| Ensembl | ENSG00000142515 | ENSMUSG00000063713 | ||||||||||||
| Uniprot | P07288 | O35307 | ||||||||||||
| Refseq | NM_001030047 (mRNA) NP_001025218 (protein) |
XM_001000656 (mRNA) XP_001000656 (protein) |
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| Location | Chr 19: 56.05 - 56.06 Mb | Chr 7: 44.06 - 44.06 Mb | ||||||||||||
| Pubmed search | [1] | [2] | ||||||||||||
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.[1][2]
Rising levels of PSA over time are associated with both localized and metastatic prostate cancer (CaP).
Contents |
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 and allows sperm to swim freely.[3] It is also believed to be instrumental in dissolving the cervical mucous cap, allowing the entry of sperm.[4]
Biochemically it is a serine protease (EC 3.4.21.77) enzyme, the gene of which is located on the nineteenth chromosome (19q13).[5]
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. The chronology of the discovery of PSA is reviewed by Rao et al. In 1960, 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.[6]
PSA is normally present in the blood at very low levels. The reference range of 0-4.0 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.[8] 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.[9] Obesity has been reported to reduce serum PSA levels.[10] Delayed early detection may partially explain worse outcomes in obese men with early prostate cancer.[11]
PSA levels can be also increased by prostate infection, irritation, benign prostatic hyperplasia (BPH), and recent ejaculation,[12][13] producing a false positive result. Digital rectal examination (DRE) has been shown in several studies[14] 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.
Despite earlier findings,[15] recent research suggests that the rate of increase of PSA (the PSA velocity) is not a more specific marker for prostate cancer.[16] 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.[17]
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. [18]
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.[19] However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours.[12]
| Fluid | PSA (ng/mL) |
|---|---|
| semen |
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| amniotic fluid |
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| breast milk |
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| saliva |
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| female urine |
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| female serum |
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It is now clear that the term prostate specific antigen is a misnomer. Although present in large amounts in prostatic tissue and semen, it has been detected in other body fluids and tissues.[20]
Other than semen, 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.[21]
Tissue samples can be stained for the presence of PSA in order to determine the origin of malignant cells that have metastasized.[22]
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).[23] Recent reports indicate that refraining from ejaculation 24 hours or more prior to testing will improve test accuracy.[12]
PSA was first identified by researchers attempting to find a substance in seminal fluid that would aid in the investigation of rape cases.[24] PSA is now used to indicate the presence of semen in forensic serology.[25] 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 spermatazoa, it remains useful in identifying semen from vasectomized and azoospermic males.[26]
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 is necessary to conclusively state that semen is present.[20] While traditional tests such as crossover electrophoresis have a sufficiently low sensitivity to only detect seminal PSA, newer diagnostics tests developed from clinical prostate cancer screening methods have lowered the threshold of detection down to 4ng/mL.[27] 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.[20] 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 (4ng/mL) test cannot conclusively identify the presence of semen, so care must be taken with the interpretation of such results.
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This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)
| PSA (abbreviation) | |
| molecular biomarker (medicine) | |
| Kallikrein (in medicine) |
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