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p57^kip2

Authors: Heba Abdelal, M.D., Natalia Buza, M.D.

Editorial Board Member: Gulisa Turashvili, M.D., Ph.D.

Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.

Last author update: 15 November 2021

Last staff update: 15 November 2021

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PubMed Search: p57[TI] kip2 pathology

Table of Contents

Cite this page: Abdelal H, Buza N. p57 kip2. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsp57kip2.html. Accessed December 26th, 2024.

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

p57 staining pattern should be described in the pathology report as retained / normal or absent / negative
Discordant p57 immunostaining patterns (p57 positive villous cytotrophoblast and p57 negative villous stromal cells or vice versa) may also occur in rare androgenetic / biparental mosaic or chimeric gestations (Am J Surg Pathol 2021 Jun 2 [Accessed 2 November 2021], Int J Gynecol Pathol 2013;32:199, Semin Diagn Pathol 2014;31:223)
Twin complete hydatidiform mole and nonmolar gestations may show an admixture of p57 negative and p57 positive chorionic villi (Am J Surg Pathol 2012;36:443)

Microscopic (histologic) images

Contributed by Natalia Buza, M.D. and Heba Abdelal, M.D.

p57 in complete hydatidiform mole

p57 in partial hydatidiform mole

p57 expression in nonmolar gestation

p57 in complete hydatidiform mole

Virtual slides

Images hosted on other servers:

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

Partial hydatidiform mole
Chromosomal trisomies
Rare cases of complete hydatidiform mole may have normal p57 expression due to retained maternal chromosome 11 (Mod Pathol 2004;17:1155, Am J Surg Pathol 2009;33:1409)

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])
- Partial hydatidiform mole with loss of maternal chromosome 11 (Am J Surg Pathol 2011;35:1586)
- Regional or complete paternal uniparental disomy (UPD) affecting chromosome 11 (Mod Pathol 2019;32:1180)
- Point mutations
- Epigenetic changes

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:
- Androgenetic / biparental mosaic or chimeric gestations (Int J Gynecol Pathol 2021;40:510)
- Complete hydatidiform mole with relaxation of genomic imprinting / incomplete genomic imprinting (Semin Diagn Pathol 2014;31:223)

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?

Loss of p57 expression, consistent with complete hydatidiform mole
Retained p57 expression, likely chromosomal trisomy
Retained p57 expression, likely nonmolar hydropic abortion
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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