Stains & CD markers
p57kip2

Editorial Board Member: Gulisa Turashvili, M.D., Ph.D.
Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.
Heba Abdelal, M.D.
Natalia Buza, M.D.

Last author update: 15 November 2021
Last staff update: 15 November 2021

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PubMed Search: p57[TI] kip2 pathology

Heba Abdelal, M.D.
Natalia Buza, M.D.
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Cite this page: Abdelal H, Buza N. p57 kip2. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsp57kip2.html. Accessed December 9th, 2022.
Definition / general
  • p57 is a cyclin dependent kinase inhibitor protein, the product of the paternally imprinted, maternally expressed gene CDKN1C (p57KIP2) located on chromosome 11p15.5
  • p57 immunohistochemical stain can be used to separate a complete hydatidiform mole from partial hydatidiform mole and nonmolar gestations
Essential features
  • Normal p57 expression (strong nuclear staining in villous cytotrophoblasts, intermediate trophoblasts and villous stromal cells) is seen in all gestations that contain maternal genetic material
  • p57 expression is lost in complete hydatidiform mole, while it is retained in partial hydatidiform moles and nonmolar specimens
  • p57 immunohistochemistry cannot distinguish between a partial hydatidiform mole and nonmolar gestations
  • Short tandem repeat (STR) genotyping can precisely classify gestations with normal / positive p57 expression and morphologic suspicion for a hydatidiform mole
Terminology
  • CDKN1C
  • p57kip2
Pathophysiology
  • p57 is a cyclin dependent kinase inhibitor protein, the product of the paternally imprinted, maternally expressed gene CDKN1C (p57KIP2) located on chromosome 11p15.5 (Lab Invest 1998;78:269)
  • Maternal genetic material and intact genomic imprinting is essential for p57 protein expression
  • Gestations containing maternal genetic material (including maternal copy of chromosome 11) - nonmolar hydropic abortions, chromosomal trisomies, digynic triploidy and partial hydatidiform moles - have normal retained p57 expression in villous cytotrophoblasts and villous stromal cells, while staining is uniformly absent in syncytiotrophoblasts (Hum Pathol 2002;33:1188, Annu Rev Pathol 2017;12:449, Arch Pathol Lab Med 2017;141:1052)
  • Complete hydatidiform moles (CHM), including very early complete moles, lack maternal genetic contribution, therefore p57 expression is typically absent in the above cell types (Semin Diagn Pathol 2014;31:223)
    • Small subset of complete hydatidiform moles (~0.6 - 2.6% of all hydatidiform moles) are familial biparental complete moles (FBCHM) and contain both maternal and paternal genomes
    • They are caused by mutations in maternal effect genes NALP7 / NLRP7 (chromosome 19q13.4) or KHDC3L (chromosome 6q13) that lead to disruption of genomic imprinting; hence, they also show lack of p57 expression (Nat Genet 2006;38:300, Hum Reprod 2015;30:159, Hum Mol Genet 1999;8:667)
  • Differential p57 expression is useful in the diagnostic distinction between complete mole and its mimics (i.e., partial moles and nonmolar hydropic abortions) (Am J Surg Pathol 2009;33:805)
  • p57 immunohistochemistry does not differentiate between partial hydatidiform moles and nonmolar gestations that mimic a partial mole morphologicaly (biparental diploid nonmolar hydropic abortions, digynic triploid gestations and chromosomal trisomies) since they contain a maternal chromosomal complement (Hum Pathol 2005;36:180)
  • Rare mosaic androgenetic / biparental gestations and twin (complete mole and nonmolar) gestations may demonstrate discordant p57 staining patterns, inconsistent with the morphology (Am J Surg Pathol 2021 Jun 2 [Accessed 2 November 2021], Int J Gynecol Pathol 2013;32:199, Semin Diagn Pathol 2014;31:223)
Interpretation
  • p57 is a nuclear stain
  • Normal p57 expression (strong nuclear staining in villous cytotrophoblasts and villous stromal cells) is seen in all gestations containing maternal genetic material
  • Syncytiotrophoblastic cells are always negative for p57, regardless of the type of gestation
  • Maternal decidua and intervillous intermediate trophoblast islands are always positive for p57, regardless of the type of gestation and can serve as internal positive control
  • Evaluation of p57 expression should focus on 2 cell types, villous cytotrophoblasts and villous stromal cells, that show differential p57 expression (i.e., absence of staining in complete hydatidiform moles)
  • Limited p57 staining (less than 10% of villous cytotrophoblast and villous stromal cells) can be seen in complete hydatidiform moles (Mod Pathol 2021;34:961)
Uses by pathologists
  • Diagnostic work up of suspected molar gestations: p57 immunostain can differentiate between a complete hydatidiform mole and its morphologic mimics (Annu Rev Pathol 2017;12:449)
Prognostic factors
  • Complete hydatidiform moles have a 20 - 25% risk of progression into persistent / invasive mole and 3 - 5% risk of gestational choriocarcinoma (Lancet 2010;376:717, BJOG 2003;110:22)
  • Risk of persistent / invasive mole and choriocarcinoma following a partial molar gestation is 4 - 5% and < 0.5%, respectively (Lancet 2010;376:717, BJOG 2003;110:22)
  • Nonmolar gestations with morphologic features mimicking hydatidiform moles do not have an associated increased risk of persistent gestational trophoblastic disease or gestational trophoblastic neoplasia
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Natalia Buza, M.D. and Heba Abdelal, M.D.
p57 in complete hydatidiform mole

p57 in complete hydatidiform mole

p57 in partial hydatidiform mole

p57 in partial hydatidiform mole

 p57 expression in nonmolar gestation

p57 expression in nonmolar gestation

p57 in complete hydatidiform mole

p57 in complete hydatidiform mole

Virtual slides

Images hosted on other servers:
p57 expression in partial mole

p57 expression in partial mole

Positive staining - normal
  • Normal biparental nonmolar gestations (Semin Diagn Pathol 2014;31:223)
    • Normal p57 expression (strong nuclear staining in villous cytotrophoblasts and villous stromal cells) is seen in all gestations containing maternal genetic material
    • Maternal decidua and intervillous intermediate trophoblast islands are always positive for p57, regardless of the type of gestation and can serve as internal positive control
Positive staining - disease
Negative staining
  • Complete hydatidiform mole, including familial biparental complete hydatidiform mole
    • Negative or limited p57 staining (less than 10% of villous cytotrophoblast and villous stromal cells)
  • Rare gestations other than complete hydatidiform mole may also be associated with loss of p57 expression (Am J Surg Pathol 2021 Jun 2 [Accessed 2 November 2021])
Discordant staining
  • p57 expression pattern is discordant when the villous cytotrophoblasts are p57 positive and villous stromal cells are p57 negative or vice versa
  • Possible underlying pathomechanisms include:
Molecular / cytogenetics description
  • Although it is not directly linked to p57 / CDKN1C, short tandem repeat (STR) genotyping can be used for precise classification of molar gestations by identifying the parental genetic contributions to their genomes (Mod Pathol 2021;34:1658, Mod Pathol 2021;34:961)
  • STR genotyping can separate between p57 positive partial hydatidiform mole and p57 positive nonmolar gestations with abnormal villous morphology (Int J Gynecol Pathol 2013;32:307)
Sample pathology report
  • Uterine contents:
    • Complete hydatidiform mole (see comment)
    • Comment: The chorionic villi are markedly enlarged and hydropic with cistern formation. Circumferential trophoblast hyperplasia and intermediate trophoblast atypia are also identified. p57 immunostain is negative in villous cytotrophoblasts and villous stromal cells, supporting the diagnosis.
  • Uterine contents:
    • Mildly hydropic, irregular chorionic villi, consistent with partial hydatidiform mole (see comment)
    • Gestational endometrium
    • No fetal parts identified
    • Comment: The chorionic villi are mildly hydropic and irregularly shaped with surface invaginations and trophoblastic pseudoinclusions. p57 immunostain shows retained expression in cytotrophoblast and villous stromal cells. Molecular genotyping results are consistent with a dispermic (heterozygous) partial hydatidiform mole (see separate addendum report).
Board review style question #1

A 32 year old woman presents with spontaneous abortion at 9 weeks estimated gestational age. Gross examination shows chorionic villous tissue with mild hydrops and there are no fetal parts identified. p57 immunostain is performed; what is your interpretation of this staining pattern?

  1. Loss of p57 expression, consistent with complete hydatidiform mole
  2. Retained p57 expression, likely chromosomal trisomy
  3. Retained p57 expression, likely nonmolar hydropic abortion
  4. Retained p57 expression, likely partial hydatidiform mole
Board review style answer #1
A. Loss of p57 expression, consistent with complete hydatidiform mole

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Reference: p57kip2
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