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Prostate specific antigen (PSA)

Reviewers: Komal Arora, M.D., Nat Pernick, M.D. (see Reviewers page)
Revised: 21 April 2012, last major update April 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.


● 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, BUT
● Routine screening using PSA with or without digital rectal exam does not significantly affect mortality overall or from prostate cancer (BMJ 2010 Sep 14;34), 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 for 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

Micro images

Bladder: ectopic prostate

Prostatic adenocarcinoma: comparison to NKX3.1, PSAP

Prostatic adenocarcinoma: metastatic to solid papillary breast carcinoma (left), testis (right)

Prostatic duct carcinoma

Prostate: neuroendocrine carcinoma is PSA+

Positive stains-normal

● Prostatic epithelium

Positive stains-disease

● Prostatic adenocarcinoma, BUT less sensitive in poorly differentiated tumors (Am J Surg Pathol 1986;10:765, Am J Surg Pathol 1982;6:553), may become negative after hormonal treatment (Hum Pathol 1996;27:1377)
● In gynecomastia, PSA is associated with antiandrogen therapy (but PSAP negative)
● Salivary gland pleomorphic adenoma (50%), salivary duct carcinoma (60%)

Negative stains

● Nephrogenic adenoma, prostatic adenoid basal tumor, adenosquamous, clear cell, small cell and squamous cell carcinomas

End of Stains > Prostate specific antigen (PSA)

Ref Updated: 3/30/12

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