An Analysis of Sex Steroid Receptors and p53 in Uterine Smooth Muscle Cell Tumors

子宫平滑肌瘤在组织学上可分为良性、恶性和交界性。这些平滑肌肿瘤的组织学异质性表明，不同类型的肿瘤在生长潜力和生长机制上可能存在差异。然而，参与这些肿瘤生长调控的分子机制还不完全清楚。探讨细胞周期调控机制在细胞生长机制中的作用。对于平滑肌肿瘤，我们利用良性和恶性的平滑肌肿瘤组织标本，研究了Ki-67、细胞周期蛋白E和A以及它们的催化伙伴细胞周期蛋白依赖性蛋白激酶CDK2和CDC2的表达。其中普通型平滑肌瘤(UL)20例，细胞性平滑肌瘤(CL)18例，奇异型平滑肌瘤(BL)8例，不明原因恶性潜能瘤(UMP)8例，滑膜肌瘤(LMS)20例。Ki-67检测到的增殖率在正常子宫肌层和子宫肌瘤(UL、CL和BL)中较低，而在LMS中显著升高。此外，Log-ranch生存分析显示，Cyclin A阳性和Cyclin E弥漫染色的LMS患者的生存期显著缩短。这些结果提示细胞周期蛋白和CDKs的表达可能参与子宫平滑肌肿瘤的生长调控。

Smooth muscle tumors of the uterus can be divided histologically into benign, malignant, and borderline types. The histological heterogeneity of these smooth muscle tumors suggests that there may be differences in growth potential as well as in growth mechanism among the various types. However, the molecular mechanisms involved in the growth regulation of these tumors are not fully understood. To investigate the cell cycle regulatory machineries involved in the growth mechanism. of smooth muscle tumors, we studied the expression of Ki-67, cyclins E and A, and their catalytic partners, the cyclin-dependent kinases cdk2 and cdc2 using tissue specimens from benign and malignant smooth muscle tumors. These included 20 cases of usual leiomyoma (UL), 18 of cellular leiomyoma (CL), 8 of bizarre leiomyoma (BL), 8 of uncertain malignant potential tumors (UMP.), and 20 of leiomyosarcorna (LMS). The proliferation rate detected by Ki-67 was low in normal myometrium and leiomyomas (UL, CL, and BL), but it was markedly increased in LMS.The expression of the cyclins (E and A), and cdks (cdk2 and cdc2) was also low in normal myometrium and leiomyomas. However, the expression of these factors was markedly increased in LMS.In addition, a survival analysis by Log-rank test revealed that those LMSs with positive staining for cyclin A and with diffusely staining for cyclin E were associated with significantly shorter survival. These results suggest that expression of cyclins and cdks may be involved in the growth control of uterine smooth muscle tumors.