CDKN1C
MIM.600856 11p15.5
The p57(KIP2) protein (P57KIP2) is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation.
The p57KIP2 gene is paternally imprinted and maternally expressed, and the presence of its protein product serves as a surrogate marker for the nuclear maternal genome.
Because a complete HM (CHM) is the only type of conceptus lacking a maternal contribution, p57KIP2 immunostaining is correspondingly absent in this entity, whereas it is present in CHM mimics (partial mole).
Pathology
germline mutations in Beckwith-Wiedemann syndrome (BWS)(MIM.130650)
Immunochemistry
The p57KIP2 gene is paternally imprinted and maternally expressed; therefore, the positive staining of its protein indicates the presence of a functional maternal allele.
Because complete hydatidiform moles (CHMs) lack a maternal genome, p57KIP2 immunostaining is absent. (#17904617#)
p57KIP2 expression in molar pregnancy
- Negative p57KIP2 immunoreactivity (paternally imprinted, maternally expressed gene) is in perfect concordance with the androgenetic origin of molar pregnancies proven by DNA polymorphism. (#15971478#)
- p57KIP2 immunoreactivity, which can be performed in routine pathologic examinations, is a diagnostic tool to differentiate androgenetic complete moles from biparental conceptuses. (#15971478#)
References
Diagnosis and subclassification of hydatidiform moles using p57 immunohistochemistry and molecular genotyping: validation and prospective analysis in routine and consultation practice settings with development of an algorithmic approach. McConnell TG, Murphy KM, Hafez M, Vang R, Ronnett BM. Am J Surg Pathol. 2009 Jun;33(6):805-17. PMID: #19145201#
Immunohistochemical expression of p57 in placental vascular proliferative disorders of preterm and term placentas. Allias F, Lebreton F, Collardeau-Frachon S, Vasiljevic A, Devouassoux-Shisheboran M, Aziza J, Jeanne-Pasquier C, Arcin-Thoury F, Patrier S. Fetal Pediatr Pathol. 2009;28(1):9-23. PMID: #19116812#
Utility of p57 protein(KIP2) in molar disease to determine its androgenetic origin. García-Barriola V, de Gómez MN, Dickson-González S, Figueira L, Cortés-Charry R. J Reprod Med. 2008 Jul;53(7):476-80. PMID: #18720921#
Hoffner L, Dunn J, Esposito N, Macpherson T, Surti U. P57KIP2 immunostaining and molecular cytogenetics: combined approach aids in diagnosis of morphologically challenging cases with molar phenotype and in detecting androgenetic cell lines in mosaic/chimeric conceptions.Hum Pathol. 2008 Jan;39(1):63-72. PMID: #17904617#
Maggiori MS, Peres LC. Morphological, immunohistochemical and chromosome in situ hybridization in the differential diagnosis of Hydatidiform Mole and Hydropic Abortion. Eur J Obstet Gynecol Reprod Biol. 2007 Dec;135(2):170-6. PMID: #17602823#
P57kip2 immunohistochemical expression and ultrastructural findings of gestational trophoblastic disease and related disorders. Soma H, Osawa H, Oguro T, Yoshihama I, Fujita K, Mineo S, Kudo M, Tanaka K, Akita M, Urabe S, Kudo Y. Med Mol Morphol. 2007 Jun;40(2):95-102. PMID: #17572845#
Popiolek DA, Yee H, Mittal K, Chiriboga L, Prinz MK, Caragine TA, Budimlija ZM. Multiplex short tandem repeat DNA analysis confirms the accuracy of p57(KIP2) immunostaining in the diagnosis of complete hydatidiform mole. Hum Pathol. 2006 Nov;37(11):1426-34. PMID: #16949913#
p57KIP2 immunostaining in the diagnosis of complete versus partial hydatidiform moles. Sebire NJ, Lindsay I. Histopathology. 2006 Jun;48(7):873-4. PMID: #16722940#
Genetic origin and imprinting in hydatidiform moles. Comparison between DNA polymorphism analysis and immunoreactivity of p57KIP2. Kihara M, Matsui H, Seki K, Nagai Y, Wake N, Sekiya S. J Reprod Med. 2005 May;50(5):307-12. PMID: #15971478#
p57KIP2 immunohistochemistry in early molar pregnancies: emphasis on its complementary role in the differential diagnosis of hydropic abortuses. Merchant SH, Amin MB, Viswanatha DS, Malhotra RK, Moehlenkamp C, Joste NE. Hum Pathol. 2005 Feb;36(2):180-6. PMID: #15754295#
Immunohistochemical characterization of p57Kip2 expression in tetraploid hydropic placentas. Fukunaga M. Arch Pathol Lab Med. 2004 Aug;128(8):897-900. PMID: #15270611#
Romaguera RL, Rodriguez MM, Bruce JH, Zuluaga T, Viciana A, Penalver MA, Mehrdad N. Molar gestations and hydropic abortions differentiated by p57 immunostaining. Fetal Pediatr Pathol. 2004 Mar-Jun;23(2-3):181-90. PMID: #15768863#
Jun SY, Ro JY, Kim KR. p57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles. Histopathology. 2003 Jul;43(1):17-25. PMID: #12823708#