title: Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, Cyclin E, p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease.
abstract: The role of cell cycle protein expression in gestational trophoblastic disease is poorly understood. In this study we investigated the immunostaining patterns of G(1) restriction point and G(1)-S regulatory proteins E2F-1, Cdk2, cyclin E, p27(kip1), and the proliferation marker Ki-67 on routinely processed sections of 29 hydatidiform moles (10 partial moles and 19 complete moles, including 9 persistent moles), 7 choriocarcinomas, and 7 normal placentas. Ki-67 trophoblast staining decreased with increasing gestational age of the placenta, and showed maximal expression in gestational trophoblastic disease. Cyclin-dependent kinase activity, as reflected by Cdk2 expression patterns, also decreased with placental maturation. E2F-1 was uniquely expressed by trophoblasts of moles and choriocarcinoma. Cyclin E was maximally expressed by complete moles and choriocarcinomas, and showed an inverse relationship with the cyclin-dependent kinase inhibitor p27(kip1). Abnormal trophoblastic proliferations may be mediated through interactions of Cdk-2, E2F-1, cyclin E, and p27(kip1). Overexpression of cyclin E was associated with more aggressive forms of gestational trophoblastic disease. However, we did not find distinguishing features between complete moles that spontaneously resolved after evacuation and persistent moles that required chemotherapy. The different expression patterns of cyclin E and E2F-1 in partial and complete moles may be useful in distinguishing these two entities. Furthermore, loss of p27(kip1) in malignant trophoblast may represent a necessary step in the development of choriocarcinoma.
authors.affiliation: Department of Pathology, Los Angeles County and University of Southern California Healthcare Network, Los Angeles, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Olvera
authors.forename: S
authors.initials: S
authors.lastname: Harris
authors.forename: C A
authors.initials: CA
authors.lastname: Amezcua
authors.forename: A
authors.initials: A
authors.lastname: McCourty
authors.forename: S
authors.initials: S
authors.lastname: Rezk
authors.forename: C
authors.initials: C
authors.lastname: Koo
authors.forename: J C
authors.initials: JC
authors.lastname: Felix
authors.forename: R K
authors.initials: RK
authors.lastname: Brynes
mesh_terms: D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D019927:Cyclin E / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D014328:Trophoblastic Neoplasms / Q000378:metabolism* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; D019927:Cyclin E; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D019394:Ki-67 Antigen; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases