Prostate specific antigen

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Current revision (12:27, 20 November 2009) (view source)
(variations on PSA)
 
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PSA is a poor [[screening]] test for [[cancer]] of the [[prostate]].
PSA is a poor [[screening]] test for [[cancer]] of the [[prostate]].
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Normal levels 0.1-4.0 ng/ml.
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PSA is a serine protease belonging to the kallarein family. It is single-chain glycoprotein coded for at 19q13.4. It is produced by prostate cells and excreted into prostatic fluid where its physiological role is to help the seminal coagulum to dissolve by proteolysis.
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PSA is a protein that is normally produced by prostate cells. The protein is found in prostatic fluid and its physiological role is to help the seminal coagulum to dissolve. It is single-chain glycoprotein coded for at 19q13.4
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Normal levels 0.1-4.0 ng/ml, though it is better to think of age-specific ranges rather than absolute cut-off values. There is an overlap between normal, benign disease and malignant disease. Attempts have been made to increase the diagnositc utility of PSA in several ways:
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*PSA velocity  - monitoring the rate of increase over a period of time)
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*PSA density - amount of PSA produced relative to the volume of prostate as measured ultrasonographically).
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*PSA fractions - measuring free PSA versus PSA bound to α-2-macroglobulin
==Limitations==
==Limitations==
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==History==
==History==
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Several proteins found only in seminal fluid were described in 1971. PSA was was subsequently isolated and characterised in 1973. <ref>One of the original papers isolation and characterising PSA. [[Pubmed:4631694|Li TS, Beling CG. Isolation and characterization of two specific antigens of human seminal plasma. Fertil Steril. 1973 Feb;24(2):134-44.]]</ref> It was named PSA in 1979 and prior to that had also been referred to as gamma seminoprotein <ref>[[Pubmed:5106556|Hara M, Koyanagi Y, Inoue T, Fukuyama T. [Some physico-chemical characteristics of " -seminoprotein", an antigenic component specific for human seminal plasma. Forensic immunological study of body fluids and secretion. VII] Nippon Hoigaku Zasshi. 1971 Jul;25(4):322-4. Japanese.]]</ref> and p30 <ref>[[Pubmed:744956|Sensabaugh GF. Isolation and characterization of a semen-specific protein from human seminal plasma: a potential new marker for semen identification. J Forensic Sci. 1978 Jan;23(1):106-15.]]</ref>. One of its earliest intended uses was as a forensic tool in rape cases. <ref>[[Pubmed:3881667|Graves HC, Sensabaugh GF, Blake ET. Postcoital detection of a male-specific semen protein. Application to the investigation of rape. N Engl J Med. 1985 Feb 7;312(6):338-43.]]</ref>
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Several proteins found only in seminal fluid were described in 1971. PSA was was subsequently isolated and characterised in 1973.<ref>One of the original papers isolation and characterising PSA. [[Pubmed:4631694|Li TS, Beling CG. Isolation and characterization of two specific antigens of human seminal plasma. Fertil Steril. 1973 Feb;24(2):134-44.]]</ref> It was named PSA in 1979 and prior to that had also been referred to as gamma seminoprotein <ref>[[Pubmed:5106556|Hara M, Koyanagi Y, Inoue T, Fukuyama T. [Some physico-chemical characteristics of " -seminoprotein", an antigenic component specific for human seminal plasma. Forensic immunological study of body fluids and secretion. VII] Nippon Hoigaku Zasshi. 1971 Jul;25(4):322-4. Japanese.]]</ref> and p30 <ref>[[Pubmed:744956|Sensabaugh GF. Isolation and characterization of a semen-specific protein from human seminal plasma: a potential new marker for semen identification. J Forensic Sci. 1978 Jan;23(1):106-15.]]</ref>. One of its earliest intended uses was as a forensic tool in rape cases. <ref>[[Pubmed:3881667|Graves HC, Sensabaugh GF, Blake ET. Postcoital detection of a male-specific semen protein. Application to the investigation of rape. N Engl J Med. 1985 Feb 7;312(6):338-43.]]</ref>
==Physiology==
==Physiology==

Current revision

PSA is a poor screening test for cancer of the prostate.

PSA is a serine protease belonging to the kallarein family. It is single-chain glycoprotein coded for at 19q13.4. It is produced by prostate cells and excreted into prostatic fluid where its physiological role is to help the seminal coagulum to dissolve by proteolysis.

Normal levels 0.1-4.0 ng/ml, though it is better to think of age-specific ranges rather than absolute cut-off values. There is an overlap between normal, benign disease and malignant disease. Attempts have been made to increase the diagnositc utility of PSA in several ways:

  • PSA velocity - monitoring the rate of increase over a period of time)
  • PSA density - amount of PSA produced relative to the volume of prostate as measured ultrasonographically).
  • PSA fractions - measuring free PSA versus PSA bound to α-2-macroglobulin

Contents

Limitations

History

Several proteins found only in seminal fluid were described in 1971. PSA was was subsequently isolated and characterised in 1973.[2] It was named PSA in 1979 and prior to that had also been referred to as gamma seminoprotein [3] and p30 [4]. One of its earliest intended uses was as a forensic tool in rape cases. [5]

Physiology

Androgen responsive elements exist in the proximal promoter region of the PSA gene. In females PSA is present at very low concentrations which is modified by corticosteroids. Interestingly higher levels are found in female hirsutism[6].

Levels in normal males are associated with

  • Individual genetics - explains 45% of variability
  • Individual parameters which unhappily only explain 23% of variability so far[7]:
    • Age
    • Transitional zone volume of prostate gland and TZ were retained in the final model. The proportion of variability in total PSA explained by these 2 factors, however, was below 24%. In contrast, estimates of heritability showed that approximately 45% of the variability in total PSA could be explained by inherited factors

PSA has a half-life in the body of about 3 days.[8]

Genetics

In man it is part of a 13 kallikrein-related gene complex with 5 pseudogenes and 5 exons.

See Also

References

  1. Eastham JA, Riedel E, Scardino PT, Shike M, Fleisher M, Schatzkin A, Lanza E, Latkany L, Begg CB; Polyp Prevention Trial Study Group. Variation of serum prostate-specific antigen levels: an evaluation of year-to-year fluctuations. JAMA. 2003 May 28;289(20):2695-700.
  2. One of the original papers isolation and characterising PSA. Li TS, Beling CG. Isolation and characterization of two specific antigens of human seminal plasma. Fertil Steril. 1973 Feb;24(2):134-44.
  3. Hara M, Koyanagi Y, Inoue T, Fukuyama T. [Some physico-chemical characteristics of " -seminoprotein", an antigenic component specific for human seminal plasma. Forensic immunological study of body fluids and secretion. VII] Nippon Hoigaku Zasshi. 1971 Jul;25(4):322-4. Japanese.
  4. Sensabaugh GF. Isolation and characterization of a semen-specific protein from human seminal plasma: a potential new marker for semen identification. J Forensic Sci. 1978 Jan;23(1):106-15.
  5. Graves HC, Sensabaugh GF, Blake ET. Postcoital detection of a male-specific semen protein. Application to the investigation of rape. N Engl J Med. 1985 Feb 7;312(6):338-43.
  6. Melegos DN, Yu H, Ashok M, Wang C, Stanczyk F, Diamandis EP. Prostate-specific antigen in female serum, a potential new marker of androgen excess. The Journal of clinical endocrinology and metabolism. 1997 Mar; 82(3):777-80.
  7. Bansal A, Murray DK, Wu JT, Stephenson RA, Middleton RG, Meikle AW. Heritability of prostate-specific antigen and relationship with zonal prostate volumes in aging twins. The Journal of clinical endocrinology and metabolism. 2000 Mar; 85(3):1272-6.
  8. http://radiology.rsnajnls.org/cgi/content/abstract/184/1/271
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