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Stains

p57kip2


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 2 December 2011, last major update December 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

General
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● Also called CDKN1C
● First described in 1995 (Genes Dev 1995;9:650)
● Strongly paternally imprinted gene on 11p15.5, expressed predominantly from the maternal allele in most tissues

Physiology
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● Genetic imprinting: differential DNA methylation of maternal and paternal alleles leading to allele-specific expression
● p57kip2 is potent cyclin-dependent cell cycle inhibitor and tumor suppressor
● Lack of p57 activity is associated with hyperproliferation in Beckwith-Wiedemann syndrome and complete hydatidiform mole (Hum Pathol 2002;33:1188)
● Methylation of p16(INK4A) followed by methylation of p57(KIP2) occurs in gastric MALT lymphoma associated with H. pylori infection (Mod Pathol 2006;19:141)
● Repressed in breast cancer cells mainly through histone modifications (PLoS One 2009;4:e5011)

Interpretation
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● Nuclear stain

Uses by Pathologists
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● Differentiate complete hydatidiform mole (no nuclear DNA of maternal origin ==> p57kip2 underexpressed) vs. partial hydatidiform mole or spontaneous abortion (p57+, Am J Surg Pathol 2001;25:1225, Am J Clin Pathol 2010;133:196), but molecular genotyping may be helpful because complete moles are rarely p57+ (Am J Surg Pathol 2009;33:1409) and partial moles are rarely p57- (Am J Surg Pathol 2011;35:1586, Am J Surg Pathol 2009;33:805)
● Identifies maternal 11p15 loss (p57-) with paternal K(ATP) mutation as predominant causative mechanism of focal hyperinsulinism (Mod Pathol 2006;19:122)

Micro images
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Various images

   
Partial (left) versus complete (right) hydatidiform mole


Complete mole with p57 staining (rare) due to retention of maternal chromosome 11


Pancreas-focal form of congenital hyperinsulinism

Positive staining - normal
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● Maternal decidua, intervillous trophoblast islands and spontaneous abortions

Positive staining - disease
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● Partial hydatidiform mole

Negative staining
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● Complete hydatidiform mole, placental mesenchymal dysplasia (loss of p57 in stromal cells of dysplastic stem villi, Fetal Pediatr Pathol 2009;28:9)

End of Stains > p57kip2


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