Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, cyclinE, p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease

The role of cell cycle protein expression in gestational trophoblastic dise ase is poorly understood. In this study we investigated the Immunostaining patterns of G(1) restriction point and G(1)-S regulatory proteins E2F-1, Cd k2, cyclin E, p27(kip1), and the proliferation marker Ki-67 on routinely pr ocessed sections of 29 hydatidiform moles (10 partial moles and 19 complete moles, Including 9 persistent moles), 7 choriocarcinomas, and 7 normal pla centas. Ki-67 trophoblast staining decreased with increasing gestational ag e of the placenta, and showed maximal expression in gestational trophoblast ic disease. Cyclin-dependent kinase activity, as reflected by Cdk2 expressi on patterns, also decreased with placental maturation. E2F-1 was uniquely e xpressed by trophoblasts of moles and choriocarcinoma. Cyclin E was maximal ly 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 spontan eously resolved after evacuation and persistent moles that required chemoth erapy. The different expression patterns of cyclin E and E2F-1 in partial a nd complete moles may be useful in distinguishing these two entities. Furth ermore, loss of P27(kip1) in malignant trophoblast may represent a necessar y step in the development of choriocarcinoma.