Prostate specific antigen
| Kallikrein-related peptidase 3
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| Identifiers
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| Symbol(s)
| KLK3; APS; KLK2A1; PSA; hK3
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| External IDs
| OMIM: 176820 MGI: 892021 Homologene: 84789
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| Gene Ontology
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| Molecular Function:
| • serine-type endopeptidase activity
• peptidase activity
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| Cellular Component:
| • extracellular region
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| Biological Process:
| • proteolysis
• negative regulation of angiogenesis
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| RNA expression pattern
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More reference expression data
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| Orthologs
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| Human
| Mouse
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| Entrez
| 354
| 16617
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| Ensembl
| ENSG00000142515
| ENSMUSG00000063713
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| Uniprot
| P07288
| O35307
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| 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
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| Pubmed search
| [1]
| [2]
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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 the most effective test currently available for the early detection of prostate cancer. Higher than normal levels of PSA are associated with both localized and metastatic prostate cancer (CaP).
Additional recommended knowledge
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 and allows sperm to swim freely.[1] It is also believed to be instrumental in dissolving the cervical mucous cap, allowing the entry of sperm.[2]
Biochemically it is a serine protease (EC 3.4.21.77) enzyme, the gene of which is located on the nineteenth chromosome (19q13). [3]
Clinical significance
Serum PSA
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.[5]
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.[6]
PSA levels can be also increased due to prostate infection, irritation, benign prostatic hypertrophy (enlargement) or hyperplasia (BPH), recent ejaculation,[7]
or digital rectal examination (DRE),[8]
in which case it may give a false positive.[9]
Despite earlier findings,[10] recent research suggests that the rate of increase of PSA (the PSA velocity) is not a more specific marker for prostate cancer.[11] 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.[12]
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.[13] However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours.[7]
Tissue PSA
In addition to measuring the PSA in blood, tissue samples can be stained for the presence of PSA in order to determine the origin of maligant cells that have metastasized.[14]
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).[15] Recent reports indicate that refraining from ejaculation 24 hours or more prior to testing will improve test accuracy.[7]
See also
- False positive/False negative
- Prostate cancer
- Prostate cancer screening
- Tumor markers
References
- ^ Steven P. Balk, Yoo-Joung Ko, Glenn J. Bubley (2003). "Biology of Prostate-Specific Antigen" (Abstract). Journal of Clinical Oncology 28 (2): 383-91. Retrieved on 2006-09-17.
- ^ "Chapter 8: What is the prostate and what is its function?", American Society of Andrology Handbook.
- ^ Lilja H. (Nov 2003). "Biology of Prostate-Specific Antigen". Urology 62 ((5 Suppl 1)): 27-33. PMID 14607215. Retrieved on 2006-09-17.
- ^ Catalona W, Partin A, Slawin K, Brawer M, Flanigan R, Patel A, Richie J, deKernion J, Walsh P, Scardino P, Lange P, Subong E, Parson R, Gasior G, Loveland K, Southwick P (1998). "Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial.". JAMA 279 (19): 1542-7. PMID 9605898.
- ^ Kolota, Gina (May 30, 2004). "It Was Medical Gospel, but It Wasn't True". The New York Times: p. 4.7.
Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr (May 27, 2004). "Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter". N Engl J Med 350 (22): 2239-46. PMID 15163773.
Carter HB (May 27, 2004). "Prostate cancers in men with low PSA levels--must we find them?". N Engl J Med 350 (22): 2292-4. PMID 15163780.
Mytrle JF, Klimley PG, Ivor L, Bruni JF (1986). "Clinical utility of prostate specific antigen (PSA) in the management of prostate cancer", Advances in Cancer Diagnostics. San Diego: Hybritech Inc.
Mytrle JF, Ivor L (1989). "Measurement of Prostate-Specific Antigen (PSA) in Serum by a Two-Site Immunometric Method (Hybritech Tandem®-R/Tandem®-E PSA)", Clinical Aspects of Prostate Cancer. Assessment of New Diagnostic and Management Procedures. Proceedings of a workshop of the Prostate Cancer Working Group of the National Cancer Institute's Organ Systems Program, held October 16-19, 1988 at Prout's Neck, Maine, U.S.A.. New York: Elsevier, pp. 161-71. ISBN 0-444-01514-0.
Mytrle JF (1989). "Normal Levels of Prostate-Specific Antigen (PSA)", Clinical Aspects of Prostate Cancer. Assessment of New Diagnostic and Management Procedures. Proceedings of a workshop of the Prostate Cancer Working Group of the National Cancer Institute's Organ Systems Program, held October 16-19, 1988 at Prout's Neck, Maine, U.S.A.. New York: Elsevier, pp. 183-9. ISBN 0-444-01514-0.
Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, Petros JA, Andriole GL (April 25, 1991). "Measurement of prostate-specific antigen in serum as a screening test for prostate cancer". N Engl J Med 324 (17): 1156-61. PMID 1707140.
Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, deKernion JB, Ratliff TL, Kavoussi LR, Dalkin BL, et al. (May 1994). "Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men". J Urol 151 (5): 1283-90. PMID 7512659.
- ^ Thompson I, Pauler D, Goodman P, Tangen C, Lucia M, Parnes H, Minasian L, Ford L, Lippman S, Crawford E, Crowley J, Coltman C (2004). "Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.". N Engl J Med 350 (22): 2239-46. PMID 15163773.
- ^ a b c Herschman JD, Smith DS, Catalona WJ (1997), " ", Urology 50 (2): 239-43,
- ^ Crawford ED, Schutz MJ, Clejan S, Drago J, Resnick MI, Chodak GW, Gomella LG, Austenfeld M, Stone NN, Miles BJ, et al (1992). "The effect of digital rectal examination on prostate-specific antigen levels". JAMA 267 (16): 2227-8. PMID 1372943.
Chybowski FM, Bergstralh EJ, Oesterling JE (1992). "The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study". J Urol 148 (1): 83-6. PMID 1377290.
Collins GN, Martin PJ, Wynn-Davies A, Brooman PJ, O'Reilly PH (1997). "The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study". J Urol 157 (5): 1744-7. PMID 9112518.
Tarhan F, Orçun A, Küçükercan I, Camursoy N, Kuyumcuoğlu U (2005). "Effect of prostatic massage on serum complexed prostate-specific antigen levels". Urology 66 (6): 1234-8. PMID 16360449.
- ^ American Cancer Society (26 July 2006). Can Prostate Cancer Be Found Early?. Detailed Guide: Prostate Cancer. Retrieved on 2006-09-14.
- ^ {Carter H, Pearson J, Metter E, Brant L, Chan D, Andres R, Fozard J, Walsh P (1992). "Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease.". JAMA 267 (16): 2215-20. PMID 1372942.
- ^ H. Ballentine Carter (2006). "Assessing Risk: Does This Patient Have Prostate Cancer?" (Editorial). Journal of the National Cancer Institute 98 (8): 506-7. Retrieved on 2006-09-14.
- ^ D'Amico A, Chen M, Roehl K, Catalona W (2004). "Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy.". N Engl J Med 351 (2): 125-35. PMID 15247353.
- ^ Catalona W, Smith D, Ornstein D (1997). "Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements.". JAMA 277 (18): 1452-5. PMID 9145717.
- ^ Chuang AY, Demarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI (2007). "Immunohistochemical Differentiation of High-grade Prostate Carcinoma From Urothelial Carcinoma" 31 (8): 1246-1255. doi:10.1097/PAS.0b013e31802f5d33. PMID 17667550.
- ^ Thompson I, Pauler D, Goodman P, Tangen C, Lucia M, Parnes H, Minasian L, Ford L, Lippman S, Crawford E, Crowley J, Coltman C (2004). "Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.". N Engl J Med 350 (22): 2239-46. PMID 15163773.
Further reading
- De Angelis G, Rittenhouse HG, Mikolajczyk SD, Blair Shamel L, Semjonow A (2007). "Twenty Years of PSA: From Prostate Antigen to Tumor Marker". Reviews in urology 9 (3): 113–23. PMID 17934568.
- Henttu P, Vihko P (1994). "Prostate-specific antigen and human glandular kallikrein: two kallikreins of the human prostate.". Ann. Med. 26 (3): 157-64. PMID 7521173.
- Diamandis EP, Yousef GM, Luo LY, et al. (2001). "The new human kallikrein gene family: implications in carcinogenesis.". Trends Endocrinol. Metab. 11 (2): 54-60. PMID 10675891.
- Lilja H (2003). "Biology of prostate-specific antigen.". Urology 62 (5 Suppl 1): 27-33. PMID 14607215.
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