Faculty Collaboration Database

Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, Cyclin E, p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease. Mod Pathol 2001 Oct;14(10):1036-42

Date

10/13/2001

Pubmed ID

11598175

DOI

10.1038/modpathol.3880432

Scopus ID

2-s2.0-0034781160 (requires institutional sign-in at Scopus site)   43 Citations

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.

Author List

Olvera M, Harris S, Amezcua CA, McCourty A, Rezk S, Koo C, Felix JC, Brynes RK

Author

Juan Felix MD Vice Chair, Director, Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

CDC2-CDC28 Kinases
Cell Cycle Proteins
Choriocarcinoma
Cyclin E
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinases
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
Female
Humans
Hydatidiform Mole
Immunohistochemistry
Ki-67 Antigen
Pregnancy
Transcription Factors
Trophoblastic Neoplasms
Tumor Suppressor Proteins
Uterine Neoplasms