Expression of cyclin e in placentas with hydropic change and gestational trophoblastic diseases: Implications for the malignant transformation of trophoblasts

BACKGROUND. Although much is known about the morphologic, cytogenetic, and clinical characters of gestational trophoblastic diseases, little information has appeared concerning the parameters related to their persistence or neoplastic transformation. Cell cycle alterations in tumor tissue were examined in this study in light of obvious changes in the clinical behavior of malignant cells. There is an increasing body of evidence suggesting that the abnormal expression of cyclins is considered one of the most important events in malignant transformation of various human cancers. Among these cell cycle regulators, the role of cyclin E in the neoplastic transformation of trophoblast populations has been poorly defined. METHODS. Using formalin fixed, paraffin embedded trophoblastic tissues, the authors investigated the expression of cyclin E by immunohistochemistry in placentas with hydropic change and gestational trophoblastic diseases. The specimens examined included tissue from 29 patients with complete hydatidiform mole, 18 patients with partial hydatidiform mole, and 6 patients with choriocarcinoma after term pregnancy or abortion. The authors also studied four cases of hydropic abortion. RESULTS. The cyclin E indexes (CEI) were as follows: 25.7% ± 6.2% for hydropic change, 35.3% ± 12.7% for triploid partial moles, 42.2% ± 13.1% for diploid/tetraploid complete moles, and 63.6% ± 9.5% for choriocarcinomas. There was a significant difference in CEI between placentas with hydropic change and partial mole (P = 0.04) and placentas with hydropic change and complete mole (P = 0.003). Choriocarcinomas had significantly higher cyclin E expression compared with placentas, partial moles, and complete moles, respectively. A significant correlation between the expression of cyclin E and S-phase fraction was observed in gestational trophoblastic diseases (rank correlation coefficient = 0.45, P < 0.05). The relation between cyclin E expression and proliferation was abrogated in placentas with hydropic change, suggesting that cyclin E up-regulation represents a genuine aberration. CONCLUSIONS. The results of this study were consistent with the concept that cyclin E overaccumulation may play an important role in the uncontrolled proliferation and neoplastic transformation of trophoblasts. (C) 2000 American Cancer Society.