细胞周期蛋白E在伴有水肿改变的胎盘及妊娠滋养细胞疾病中的表达：对滋养细胞恶性转化的意义

Kim Y T, Cho N H, Ko J H, Yang W I, Kim J W, Choi E K, Lee S H

Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea.

Cancer. 2000 Aug 1;89(3):673-9. doi: 10.1002/1097-0142(20000801)89:3<673::aid-cncr24>3.0.co;2-r.

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.

背景

尽管对于妊娠滋养细胞疾病的形态学、细胞遗传学和临床特征已有很多了解，但关于与其持续存在或肿瘤转化相关的参数的信息却很少。鉴于恶性细胞临床行为的明显变化，本研究对肿瘤组织中的细胞周期改变进行了检测。越来越多的证据表明，细胞周期蛋白的异常表达被认为是各种人类癌症恶性转化中最重要的事件之一。在这些细胞周期调节因子中，细胞周期蛋白E在滋养细胞群体肿瘤转化中的作用尚未明确界定。

方法

作者使用福尔马林固定、石蜡包埋的滋养细胞组织，通过免疫组织化学方法研究了细胞周期蛋白E在有水肿改变胎盘和妊娠滋养细胞疾病中的表达。所检查的标本包括29例完全性葡萄胎患者、18例部分性葡萄胎患者以及6例足月妊娠或流产后绒毛膜癌患者的组织。作者还研究了4例水肿性流产病例。

结果

细胞周期蛋白E指数（CEI）如下：水肿改变为25.7%±6.2%，三倍体部分性葡萄胎为35.3%±12.7%，二倍体/四倍体完全性葡萄胎为42.2%±13.1%，绒毛膜癌为63.6%±9.5%。有水肿改变的胎盘与部分性葡萄胎之间的CEI有显著差异（P = 0.04），有水肿改变的胎盘与完全性葡萄胎之间也有显著差异（P = 0.003）。绒毛膜癌的细胞周期蛋白E表达分别显著高于胎盘、部分性葡萄胎和完全性葡萄胎。在妊娠滋养细胞疾病中，观察到细胞周期蛋白E表达与S期分数之间存在显著相关性（等级相关系数 = 0.45，P < 0.05）。在有水肿改变的胎盘中，细胞周期蛋白E表达与增殖之间的关系被消除，这表明细胞周期蛋白E上调代表一种真正的异常。