Differential expression of p57kip2, a maternally imprinted cdk inhibitor, in normal human placenta and gestational trophoblastic disease.
Evidence has recently been provided to support a role for genomic imprinting in the regulation of embryonic implantation and development and placental growth, as well as in the pathogenesis of proliferative trophoblastic diseases. The cyclin-dependent kinase inhibitor p57KIP2 has recently been recognized as a maternally imprinted gene. We investigated p57KIP2 expression in first-trimester normal placentas from interrupted pregnancy, spontaneous abortions, and different types of proliferative trophoblastic diseases using single- and double-marker immunohistochemical techniques. In normal placenta, nuclear p57KIP2 expression was observed at high frequency (up to 100%) in extravillous trophoblast, cytotrophoblast, and implantation-site interstitial trophoblast, but was absent in syncytiotrophoblast. p57KIP2 was also expressed in the stromal cells of maternal decidua, which was one of the few adult tissues retaining p57KIP2 expression (most other adult tissues investigated were negative). p57KIP2 expression was either absent or low in all cases of diploid/tetraploid complete moles (20 cases) and in three cases of gestational choriocarcinoma. On the other hand, all spontaneous abortions (12 cases) and triploid partial moles (19 cases) showed p57KIP2 levels comparable to those observed in normal placenta. These findings are in line with the hypothesis that deregulation of genomic imprinting, particularly the loss of cell-cycle inhibitors such as p57KIP2, is involved in the abnormal development of androgenetic trophoblastic proliferations. In addition, this simple immunohistochemical analysis could provide a useful diagnostic marker in difficult cases.
Chilosi
M
M
Istituto di Anatomia Patologica, University of Verona, Italy.
Piazzola
E
E
Lestani
M
M
Benedetti
A
A
Guasparri
I
I
Granchelli
G
G
Aldovini
D
D
Leonardi
E
E
Pizzolo
G
G
Doglioni
C
C
Menestrina
F
F
Mariuzzi
G M
GM
D002822:Choriocarcinoma / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D006828:Hydatidiform Mole / Q000378:metabolism; D009035:Mothers; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000378:metabolism*; D012016:Reference Values; D014328:Trophoblastic Neoplasms / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism*
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D018844:Cyclin-Dependent Kinases