Stains & molecular markers
Prostate specific antigen (PSA)

Topic Completed: 1 April 2012

Minor changes: 8 September 2020

Copyright: 2002-2020,, Inc.

PubMed Search: Prostate specific antigen [title]

Komal Arora, M.D.
Page views in 2019: 4,002
Page views in 2020 to date: 3,064
Cite this page: Arora K. Prostate specific antigen (PSA). website. Accessed September 21st, 2020.
Definition / general
  • Kallikrein related serine protease produced by secretory epithelium, drains into ductal system
  • Cleaves and liquefies seminal coagulum formed after ejaculation
Clinical features
  • Serum PSA > 4 seen in 80% with histologically documented cancer but also in 25 - 30% with nodular hyperplasia, prostatitis, infarcts, prostatic massage, cystoscopy
  • Elevated in 2 of 18 post-race marathon runners (Arch Pathol Lab Med 2003;127:345)
  • Serum PSA may be normal in prostatic duct carcinomas
  • Prostate carcinomas secrete 10x the PSA of normal tissue (in the past, 50% had levels > 10 mg/ml)
    • As a result, annual testing was traditionally recommended for men 50+ and men 40+ at increased risk
  • Routine screening using PSA with or without digital rectal exam does not significantly affect mortality overall or from prostate cancer (BMJ 2010;341:c4543), so unclear if modest benefit of reduced mortality outweighs the harms of overdetection and overtreatment (Ann Intern Med 2008;149:185, Curr Opin Urol 2010;20:185)
  • American College of Preventive Medicine does not recommend routine population screening with digital rectal exam or PSA (Am J Prev Med 2008;34:164)
  • Serial PSA measurements important for follow up
  • PSA can be performed in Point of Care setting (Clin Chim Acta 2009;406:18)
  • Related clinical tests: PSA density (PSA per volume of prostate gland), PSA velocity (changes in PSA with time), % free PSA (unbound PSA compared to alpha-1-antichymotrypsin)
  • Markers that may complement PSA in the early detection of prostate cancer include specific isoforms of PSA and PCA3
  • In patients with PSA >10 but no known prostatic carcinoma, soy isoflavones and curcumin reduced PSA levels (Prostate 2010;70:1127)
Uses by pathologists
  • Glycoprotein detected in benign and malignant prostate tissue
    • Identifies prostatic origin of most metastatic tumors, differentiates between prostatic and urothelial carcinomas
    • Non-prostate tumors are usually weak / negative for PSA / PAP
  • PSA is more sensitive (intense, diffuse staining) and specific than PAP
Microscopic (histologic) images

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Bladder, ectopic prostate

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Prostatic adenocarcinoma, comparison to NKX3.1, PSAP

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Prostatic duct carcinoma

Positive staining - normal
  • Prostatic epithelium
Positive staining - disease
Negative staining
  • Nephrogenic adenoma, prostatic adenoid basal tumor, adenosquamous, clear cell, small cell and squamous cell carcinomas
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