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Prostate

Prostatic carcinoma

Immunohistochemistry


Reviewers: Komal Arora, M.D., (see Reviewers page)
Revised: 11 August 2012, last major update February 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

AMACR / P504S
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● See also AMACR topic in Stains chapter
● Gene encodes protein involved in beta-oxidation of branched chain fatty acids
● Relatively sensitive and specific for prostatic adenocarcinoma vs. benign lesions / mimics (Am J Surg Pathol 2001;25:1397)
● Recommended to use with high molecular weight cytokeratin (Am J Surg Pathol 2002;26:1588)

CK903 / 34 beta E12 / high molecular weight cytokeratin
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● See also Cytokeratin 34 beta E12 topic in Stains chapter
● Basal cell specific anti-keratin monoclonal antibody (originally raised against human stratum corneum) which is not present next to carcinomatous glands but is present next to normal glands (usually an internal positive control is present even on biopsies)
● Positive staining rules out cancer; negative staining cannot be the sole criteria for diagnosing cancer
● Use of intervening unstained slides for immunohistochemistry recommended (Am J Surg Pathol 1999;23:567)
● Optimize with pretreatment of citrate buffer on a hot plate (may give weak staining focally in cancer cells) or steam heat and EDTA buffer; others use pepsin predigestion or microwave (Mod Pathol 1999;12:472)
● Not useful in differentiating high grade PIN from invasive carcinoma due to negative / discontinuous staining in high grade PIN

Cautions:
● False negative staining in 5% of benign acini after pepsin predigestion; due to inflamed acini, atypical adenomatous hyperplasia, postatrophic hyperplasia, atrophy; may be negative / discontinuous in high grade PIN, basal cell carcinoma / adenoid cystic carcinoma
● Most benign peripheral acini in a lobule (furthest from large duct) are CK903 negative (Am J Clin Pathol 1999;112:69)
● In TURP specimens, CK903 only stains basal cells in normal glands in 25% of specimens; can restore keratin antigenicity using low pH citrate buffer and microwave heat technique (Arch Pathol Lab Med 2000;124:1764)
● Rare strong positivity in <1% of tumor cells in lymph node metastases (Am J Surg Pathol 1999;23:147)


   
CK903 / 34 beta E12 / high molecular weight cytokeratin


ERG
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● See Stains chapter

Fatty Acid Synthetase
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● Positive marker, may supplement AMACR (Am J Clin Pathol 2011;136:239)

p63
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● See also p63 topic in Stains chapter
● Homologue of tumor suppressor gene, p53
● Expressed in basal cell component of epithelium in a variety of human tissues and appears to be important in epithelial embryogenesis
● No staining is seen in malignant glands, and the basal cells in benign glands show nuclear positivity (Mod Pathol 2002;15:1302)
Note: Rarely, aberrant diffuse expression of p63 in prostate carcinoma cells has been seen (Am J Surg Pathol 2008;32:461)

Prostate specific antigen (PSA) / Prostatic acid phosphatase (PAP)
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● Positive in tumor and benign cells; identifies prostatic origin of most metastatic tumors, differentiates between prostatic and urothelial carcinomas
● PSA more sensitive (intense, diffuse staining) and specific than PAP
● PSA present in endoplasmic reticulum, vesicles, vacuoles, lumina, while PAP is localized to lysosomal granules
● PSA/PAP less sensitive in poorly differentiated adenocarcinoma (Am J Surg Pathol 1986;10:765, Am J Surg Pathol 1982;6:553)
● PSA/PAP may become negative after hormonal treatment (Hum Pathol 1996;27:1377)
● Non-prostate tumors usually are negative or weak with PSA/PAP
● Bladder adenocarcinomas and rectal carcinomas may be strongly PAP+ but PSA-
● Rectal carcinoids also positive for PAP, perhaps due to shared cloacal derivation of rectum and prostate (Am J Surg Pathol 1991;15:785)

Other
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Other positive stains: Low molecular weight cytokeratin, CD57/Leu7, B72.3, EMA (80%), CEA (25%), cathepsin D (50%)
Other negative stains: thrombomodulin (Am J Surg Pathol 2003;27:519), CK7, CK20 (Mod Pathol 2000;13:962), MUC6 , CD10 with Gleason 2 & 3 patterns (Hum Pathol 2003;34:450)
Gleason 8-10 adenocarcinomas: usually have negative or focal (<25%) staining for CK7 and CK20, may be PSA and PAP negative, and are negative for CK 5/6, CK17, WT1, CA125, TTF-1 and villin (Am J Clin Pathol 2002;117:471); may be CD10+ (Hum Pathol 2003;34:450)

End of Prostate > Prostatic carcinoma > Immunohistochemistry


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