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Stains

AMACR

Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 15 June 2012, last major update June 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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● Alpha Methyl Acyl Coenzyme A Racemase; also called P504S
● Identified from prostate adenocarcinoma by cDNA library subtraction, coupled with high throughput microarray screening of human prostatic tissue
● A mitochondrial and peroxisomal enzyme involved in beta-oxidation of dietary branched-chain fatty acids and fatty acid derivatives (including bile acid intermediates)
● AMACR deficiency is rare cause of cerebellar ataxia (Neurology 2011;76:1768)

Uses by pathologists
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● Cytoplasmic immunohistochemical stain
● Sensitive (82-95%) and relatively specific for prostate carcinoma vs. benign prostate (Am J Surg Pathol 2001;25:1397, Am J Surg Pathol 2002;26:1588); staining is strongly positive and usually diffuse, regardless of Gleason grade
● Note: less sensitive for prostatic adenocarcinoma in Japanese patients (Prostate 2012 May 16 [Epub ahead of print])
● Most specific if circumferential luminal to subluminal and diffuse cytoplasmic staining
● Identify small foci of prostatic adenocarcinoma, in conjunction with 34betaE12 or p63 (Am J Surg Pathol 2002;26:1169)
● Used with triple stain (p63 and 34betaE12, Am J Clin Pathol 2005;123:231) or in various combinations of other markers (with CK5/6: Am J Clin Pathol 2009;132:211; with p63 for destained H&E-stained sections: Am J Clin Pathol 2005;124:708)
● Triple stain may be helpful in assessing crushed surgical margins (J Clin Pathol 2012;65:437)
● May identify a subset of atypical adenomatous hyperplasia with a premalignant potential (Am J Surg Pathol 2002;26:921)
● Note: benign prostate is usually negative or only focal / weakly positive; however, partial atrophy and crowded benign glands may be positive (Am J Surg Pathol 2005;29:874)

Micro images
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Bladder: primary adenocarcinoma (fig 3a: diffusely+) vs. secondary from colorectum (fig 3b: focal+)


Colonic adenoma

           
Prostate: microfoci of adenocarcinoma


Prostate: post-radiation adenocarcinoma


Prostate: suspicious for adenocarcinoma

   
Prostate: PIN-4 cocktail (AMACR, p63, 34betaE12) in prostatic adenocarcinoma

       
Prostate: high grade PIN


Prostate: adenosis


Quality control for AMACR staining

Positive staining - disease
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● Colon adenomas with high grade dysplasia (63%, World J Gastroenterol 2010;16:2476); colorectal adenocarcinoma
● Prostate: adenocarcinoma and high grade PIN; partial prostatic atrophy and crowded benign prostatic glands may be positive (Am J Surg Pathol 2005;29:890)
● Esophagus: Barrett related dysplasia (93%-high grade, 44%-low grade, Appl Immunohistochem Mol Morphol 2008;16:447)
● Liver: dysplasia and hepatocellular carcinoma (Appl Immunohistochem Mol Morphol 2006;14:411)
● Renal cell carcinoma-papillary type (83%, World J Urol 2011 Oct 19 [Epub ahead of print])
● Also overexpressed in lymphomas; cervical adenocarcinoma; breast, gastric, liver carcinomas; also urothelial carcinoma (30%), primary (65%) and secondary (from colorectum) bladder adenocarcinomas (Am J Surg Pathol 2002;26:921)

Negative staining
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● Benign prostate (usually, see exceptions under positive staining)
● Normal appearing small and large intestinal mucosa
● Atypical adenomatous hyperplasia (usually, 10% are positive, Am J Surg Pathol 2002;26:921)
● Ovarian carcinoma (usually, 10% are positive, Virchows Arch 2011;459:91)
● Small intestinal adenocarcinoma (usually, 4-6% are positive, Am J Surg Pathol 2005;29:890)

End of Stains > AMACR

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