View source for Prostate specific antigen

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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
 | image =  
 | image_source =  
 | PDB = 
 | Name = Kallikrein-related peptidase 3
 | HGNCid = 6364
 | Symbol = KLK3
 | AltSymbols =; APS; KLK2A1; PSA; hK3
 | OMIM = 176820
 | ECnumber =  
 | Homologene = 84789
 | MGIid = 892021
 | GeneAtlas_image1 = PBB_GE_KLK3_204582_s_at_tn.png
 | GeneAtlas_image2 = PBB_GE_KLK3_204583_x_at_tn.png
 | Function = {{GNF_GO|id=GO:0004252 |text = serine-type endopeptidase activity}} {{GNF_GO|id=GO:0008233 |text = peptidase activity}} 
 | Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} 
 | Process = {{GNF_GO|id=GO:0006508 |text = proteolysis}} {{GNF_GO|id=GO:0016525 |text = negative regulation of angiogenesis}} 
 | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 354
    | Hs_Ensembl = ENSG00000142515
    | Hs_RefseqProtein = NP_001025218
    | Hs_RefseqmRNA = NM_001030047
    | Hs_GenLoc_db =  
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 56049983
    | Hs_GenLoc_end = 56055832
    | Hs_Uniprot = P07288
    | Mm_EntrezGene = 16617
    | Mm_Ensembl = ENSMUSG00000063713
    | Mm_RefseqmRNA = XM_001000656
    | Mm_RefseqProtein = XP_001000656
    | Mm_GenLoc_db =  
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 44056315
    | Mm_GenLoc_end = 44060494
    | Mm_Uniprot = O35307
  }}
}}
{{Search infobox}}
{{SCC}}

==Overview==

'''Prostate specific antigen''' ('''PSA''') is a protein produced by the cells of the [[prostate]] gland. PSA is present in small quantities in the [[Blood plasma|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 [[metastasis|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]] and allows [[spermatozoon|sperm]] to swim freely.<ref>{{cite journal | title = Biology of Prostate-Specific Antigen | last = Steven P. Balk, Yoo-Joung Ko, Glenn J. Bubley  | journal = Journal of Clinical Oncology | volume = 28 | issue = 2 | date = 2003 | pages = 383-91 | accessdate = 2006-09-17 |format = Abstract | url =http://www.jco.org/cgi/content/full/21/2/383}}</ref> It is also believed to be instrumental in dissolving the cervical mucous cap, allowing the entry of sperm.<ref>{{cite book | title=American Society of Andrology Handbook | chapter=Chapter 8: What is the prostate and what is its function? | chapterurl=http://www.andrologysociety.com/resources/handbook/ch.8.asp | accessdate=2006-09-17}}</ref>

Biochemically it is a [[serine protease]] ({{EC number|3.4.21.77}}) [[enzyme]], the [[gene]] of which is located on the nineteenth [[chromosome]] (19q13). <ref>{{cite journal | title = Biology of Prostate-Specific Antigen | author = Lilja H.  | journal = Urology | volume = 62 | issue = (5 Suppl 1) | year = 2003 | month=Nov | pages = 27-33 | accessdate = 2006-09-17 | id = PMID 14607215}}</ref>

==Clinical significance==
===Serum PSA===
[[Image:free_psa.png|thumb|left|300px|Risk of prostate cancer in two age groups based on '''Free PSA''' as % of Total PSA <ref>{{cite journal | author = 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 | title = Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial. | journal = JAMA | volume = 279 | issue = 19 | pages = 1542-7 | year = 1998 | id = PMID 9605898}}</ref>]]

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.<!--
 --><ref name="Kolota 2004">{{cite journal |author=Kolota, Gina |month=May 30, |year=2004 |title=It Was Medical Gospel, but It Wasn't True  |journal=The New York Times |pages=p. 4.7 |url=http://query.nytimes.com/gst/fullpage.html?res=9F05E5DD1E3EF933A05756C0A9629C8B63}}<br>
                            {{cite journal |author=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 |month= May 27, |year=2004 |title=Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter |journal=[[New England Journal of Medicine|N Engl J Med]] |volume=350 |issue=22 |pages=2239-46 |id=PMID 15163773}}<br>
                            {{cite journal |author=Carter HB |month= May 27, |year=2004 |title=Prostate cancers in men with low PSA levels--must we find them? |journal=[[New England Journal of Medicine|N Engl J Med]] |volume=350 |issue=22 |pages=2292-4 |id=PMID 15163780}}<br>
                            {{cite book |author=Mytrle JF, Klimley PG, Ivor L, Bruni JF |year=1986 |chapter=Clinical utility of prostate specific antigen (PSA) in the management of prostate cancer |title=Advances in Cancer Diagnostics |location=San Diego |publisher=Hybritech Inc}}<br>
                            {{cite book |author=Mytrle JF, Ivor L |year=1989 |chapter=Measurement of Prostate-Specific Antigen (PSA) in Serum by a Two-Site Immunometric Method (Hybritech Tandem®-R/Tandem®-E PSA) |editors=Catalona WJ, Coffey DS, Karr JP (eds.) |title=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. |location=New York |publisher=Elsevier |isbn=0-444-01514-0 |pages=pp. 161-71}}<br>
                            {{cite book |author=Mytrle JF |year=1989 |chapter=Normal Levels of Prostate-Specific Antigen (PSA) |editors=Catalona WJ, Coffey DS, Karr JP (eds.) |title=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. |location=New York |publisher=Elsevier |isbn=0-444-01514-0 |pages=pp. 183-9}}<br>
                            {{cite journal |author=Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, Petros JA, Andriole GL |month= April 25, |year=1991 |title=Measurement of prostate-specific antigen in serum as a screening test for prostate cancer |journal=[[New England Journal of Medicine|N Engl J Med]] |volume=324 |issue=17 |pages=1156-61 |id=PMID 1707140}}<br>
                            {{cite journal |author=Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, deKernion JB, Ratliff TL, Kavoussi LR, Dalkin BL, et al. |month= May |year=1994 |title=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 |journal=J Urol |volume=151 |issue=5 |pages=1283-90 |id=PMID 7512659}}</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>{{cite journal | author = Thompson I, Pauler D, Goodman P, Tangen C, Lucia M, Parnes H, Minasian L, Ford L, Lippman S, Crawford E, Crowley J, Coltman C | title = Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. | journal = N Engl J Med | volume = 350 | issue = 22 | pages = 2239-46 | year = 2004 | id = PMID 15163773}}</ref>

PSA levels can be also increased due to [[prostate infection]], irritation, [[benign prostatic hypertrophy]] (enlargement) or [[hyperplasia]] (BPH), recent ejaculation,<ref name=ejac>{{Citation | last = Herschman JD, Smith DS, Catalona WJ | title = Effect of ejaculation on serum total and free prostate-specific antigen concentrations | url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9255295&dopt=Citation |  journal = Urology  | volume = 50 (2) | pages = 239-43 | year = 1997 }}</ref>
or [[digital rectal examination]] (DRE),<!--
 --><ref name="DRE">{{cite journal |author=Crawford ED, Schutz MJ, Clejan S, Drago J, Resnick MI, Chodak GW, Gomella LG, Austenfeld M, Stone NN, Miles BJ, et al |year=1992 |title=The effect of digital rectal examination on prostate-specific antigen levels |journal=[[Journal of the American Medical Association|JAMA]] |volume=267 |issue=16 |pages=2227-8 |id=PMID 1372943}}<br>
                {{cite journal |author=Chybowski FM, Bergstralh EJ, Oesterling JE |year=1992 |title=The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study |journal=J Urol |volume=148 |issue=1 |pages=83-6 |id=PMID 1377290}}<br>
                {{cite journal |author=Collins GN, Martin PJ, Wynn-Davies A, Brooman PJ, O'Reilly PH |year=1997 |title=The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study |journal=J Urol |volume=157 |issue=5 |pages=1744-7 |id=PMID 9112518}}<br>
                {{cite journal |author=Tarhan F, Orçun A, Küçükercan I, Camursoy N, Kuyumcuoğlu U |year=2005 |title=Effect of prostatic massage on serum complexed prostate-specific antigen levels |journal=Urology |volume=66 |issue=6 |pages=1234-8 |id=PMID 16360449}}</ref>
in which case it may give a [[false positive]].<ref>{{cite web | author=American Cancer Society | title= Can Prostate Cancer Be Found Early? | work=Detailed Guide: Prostate Cancer | url=http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_Can_prostate_cancer_be_found_early_36.asp | date=26 July 2006 | accessdate=2006-09-14}}</ref>

Despite earlier findings,<ref>{{{cite journal | author = Carter H, Pearson J, Metter E, Brant L, Chan D, Andres R, Fozard J, Walsh P | title = Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. | journal = JAMA | volume = 267 | issue = 16 | pages = 2215-20 | year = 1992 | id = 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>{{cite journal | author= H. Ballentine Carter | title = Assessing Risk: Does This Patient Have Prostate Cancer? | journal = Journal of the National Cancer Institute | volume = 98 | issue = 8 | pages = 506-7 | date = 2006 | url = http://jncicancerspectrum.oxfordjournals.org/cgi/content/full/jnci;98/8/506 | format = Editorial | accessdate = 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 retropubic prostatectomy|radical prostatectomy]].<ref>{{cite journal | author = D'Amico A, Chen M, Roehl K, Catalona W | title = Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. | journal = N Engl J Med | volume = 351 | issue = 2 | pages = 125-35 | year = 2004 | id = 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 [[Biopsy|biopsies]] in men with PSA levels between 4 and 10 ng/mL.<ref>{{cite journal | author = Catalona W, Smith D, Ornstein D | title = 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. | journal = JAMA | volume = 277 | issue = 18 | pages = 1452-5 | year = 1997 | id = PMID 9145717}}</ref> However, both total and free PSA increase immediately after ejaculation, returning slowly to baseline levels within 24 hours.<ref name=ejac/>

===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.<ref name="pmid17667550">{{cite journal |author=Chuang AY, Demarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI |title=Immunohistochemical Differentiation of High-grade Prostate Carcinoma From Urothelial Carcinoma |journal= |volume=31 |issue=8 |pages=1246-1255 |year=2007 |pmid=17667550 |doi=10.1097/PAS.0b013e31802f5d33}}</ref>

==Prostate cancer screening==
{{main|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 [[medical ultrasonography|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).<ref>{{cite journal | author = Thompson I, Pauler D, Goodman P, Tangen C, Lucia M, Parnes H, Minasian L, Ford L, Lippman S, Crawford E, Crowley J, Coltman C | title = Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. | journal = N Engl J Med | volume = 350 | issue = 22 | pages = 2239-46 | year = 2004 | id = PMID 15163773}}</ref> Recent reports indicate that refraining from ejaculation 24 hours or more prior to testing will improve test accuracy.<ref name=ejac/>

==See also==
* [[Type I and type II errors|False positive/False negative]]
* [[Prostate cancer]]
* [[Prostate cancer screening]]
* [[Tumor markers]]

==References==
{{reflist|2}}

==Further reading==
{{refbegin | 2}}
*{{cite journal |author=De Angelis G, Rittenhouse HG, Mikolajczyk SD, Blair Shamel L, Semjonow A |title=Twenty Years of PSA: From Prostate Antigen to Tumor Marker |journal=Reviews in urology |volume=9 |issue=3 |pages=113–23 |year=2007 |pmid=17934568 |doi=}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=Henttu P, Vihko P |title=Prostate-specific antigen and human glandular kallikrein: two kallikreins of the human prostate. |journal=Ann. Med. |volume=26 |issue= 3 |pages= 157-64 |year= 1994 |pmid= 7521173 |doi=  }}
*{{cite journal  | author=Diamandis EP, Yousef GM, Luo LY, ''et al.'' |title=The new human kallikrein gene family: implications in carcinogenesis. |journal=Trends Endocrinol. Metab. |volume=11 |issue= 2 |pages= 54-60 |year= 2001 |pmid= 10675891 |doi=  }}
*{{cite journal  | author=Lilja H |title=Biology of prostate-specific antigen. |journal=Urology |volume=62 |issue= 5 Suppl 1 |pages= 27-33 |year= 2003 |pmid= 14607215 |doi=  }}
}}
{{refend}}

==External links==
* American Cancer Society: Detailed Guide: Prostate Cancer [http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_Can_prostate_cancer_be_found_early_36.asp Can Prostate Cancer Be Found Early?]
* National Cancer Institute: [http://www.cancer.gov/cancertopics/factsheet/Detection/PSA The Prostate-Specific Antigen (PSA) Test: Questions and Answers]
* {{MeshName|Prostate-Specific+Antigen}}
* {{eMedicineDictionary|Prostate-Specific+Antigen}}

{{Serine endopeptidases}}
{{Tumor markers}}

[[Category:Andrology]]
[[Category:Urology]]
[[Category:Tumor markers]]
[[Category:EC 3.4.21]]
[[Category:Oncology stub]]
[[de:Prostataspezifisches Antigen]]
[[es:Antígeno prostático específico]]
[[fr:Antigène prostatique spécifique]]
[[hr:Antigen specifičan za prostatu]]
[[it:Semenogelasi]]
[[nl:Prostaatspecifiek antigen]]
[[ja:前立腺特異抗原]]
[[pl:PSA (antygen)]]
[[pt:Antígeno prostático específico]]
[[sv:Prostataspecifikt antigen]]
[[zh:前列腺特异抗原]]
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