Prostate specific antigen

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kallikrein-related peptidase 3
Identifiers
Symbol(s)	KLK3 APS
Entrez	354
OMIM	176820
RefSeq	NM_145864
UniProt	P07288
Other data
Locus	Chr. 19 q13.41

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).

1 Biochemistry
2 Clinical significance
3 Prostate cancer screening
4 See also
5 Footnotes
6 External links

[edit] Biochemistry

Prostate specific antigen (PSA), also known as kallikrein III, seminin, semenogelase, γ-seminoprotein and P-30 antigen) is a 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.<ref>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.</ref> It is also believed to be instrumental in dissolving the cervical mucous cap, allowing the entry of sperm.<ref> “Chapter 8: What is the prostate and what is its function?”, American Society of Andrology Handbook. Retrieved on 2006-09-17.</ref>

Biochemically it is a serine protease (EC 3.4.21.77) enzyme, the gene of which is located on the nineteenth chromosome (19q13). <ref>Lilja H. (Nov 2003). "Biology of Prostate-Specific Antigen". Urology 62 ((5 Suppl 1)): 27-33. PMID 14607215. Retrieved on 2006-09-17.</ref>

[edit] Clinical significance

Image:Free psa.png

PSA is normally present in the blood at very low levels; normal PSA levels are defined as between 0-4.0 ng per milliliter.<ref>Myrtle JF. (1989). “Normal levels of prostate-specific antigen (PSA)”, Edited by WJ Catalona, DS Coffey, JP Karr: Clinical aspects of prostate cancer: assessment of new diagnostic and management procedures. New York: Elsevier, 183–9.</ref> 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.<ref>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.</ref> PSA levels can be also elevated due to prostate infection, irritation, benign prostatic hypertrophy (enlargement) or hyperplasia (BPH) or recent ejaculation, in which case it may give a false positive. <ref>American Cancer Society (26 July 2006). Can Prostate Cancer Be Found Early?. Detailed Guide: Prostate Cancer. Retrieved on 2006-09-14.</ref> It is a myth that digital rectal exam raises PSA. <ref name="Kumar">Kumar and Clark, Sixth Edition, Elsevier Saunders, 2005, p. 685.</ref>

Despite earlier findings,<ref>{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.</ref> recent research suggests that the rate of increase of PSA (the PSA velocity) is not a more specific marker for prostate cancer.<ref>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.</ref> 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.<ref>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.</ref>

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.<ref>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.</ref>

[edit] 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, 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 no elevation in PSA will have prostate cancer).<ref>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.</ref>

The current guidelines of the American Cancer Society recommend that men over age 50 should be screened by a digital rectal exam and PSA every year. <ref>National Guideline Clearinghouse. Recommendations from the American Cancer Society Workshop on Early Prostate Cancer Detection. Retrieved on 2006-09-14.</ref> African-American men and those with a family history of prostate cancer should be screened annually upon reaching 45 years. Other racial and ethnic groups, such as Asian- and Hispanic-Americans have a lower risk of prostate cancer, and may not benefit from screening. Screening is likely not useful for men over age 70 or with other significant medical problems and a life expectancy of fewer than 10 years. The U.S. Preventive Services Task Force (USPSTF) concluded that "the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing". <ref>U.S. Preventive Services Task Force (December 2002)). Screening for Prostate Cancer. Retrieved on 2006-09-14.</ref> However, PSA screening is common even among older men for whom benefit is least clear.<ref>Scales C, Curtis L, Norris R, Schulman K, Albala D, Moul J (2006). "Prostate specific antigen testing in men older than 75 years in the United States.". J Urol 176 (2): 511-4. PMID 16813879.</ref>

These guidelines may be changing. A new European study has shown that a thorough screening for prostate cancer every 4 years is adequate. The screening comprises a PSA blood test, a digital rectal exam, and a transrectal ultrasound. "Very few, if any, aggressive prostate cancers escape (this) screening."<ref>Schröder F, Raaijmakers R, Postma R, van der Kwast T, Roobol M (2005). "4-year prostate specific antigen progression and diagnosis of prostate cancer in the European Randomized Study of Screening for Prostate Cancer, section Rotterdam.". J Urol 174 (2): 489-94; discussion 493-4. PMID 16006878.</ref>