P16^(INK4A)、CDK4和cyclin D1在子宫平滑肌肿瘤中的表达

Expression of P16^(INK4A), CDK4 and cyclin D1 protein in uterine smooth muscle tumors

目的:探讨P16INK4A、CDK4和细胞周期蛋白D1(cyclin D1)在子宫平滑肌肿瘤中的表达及意义。方法:应用免疫组化SP法及原位杂交法检测P16INK4A、CDK4和cyclin D1蛋白和P16INK4A mRNA在21例子宫平滑肌肉瘤(leiomyosarcoma,LMS)、34例子宫平滑肌瘤(leiomyoma,LMA)和22例正常子宫平滑肌组织中的表达情况。结果:P16INK4A、CDK4和cyclin D1蛋白在LMS、LMA和正常平滑肌组织中的阳性率分别为62%、90%、57%;15%、26%、53%;10%、10%、0%。P16INK4A、CDK4在LMS和LMA间的表达差异均有统计学意义(P<0.05);cyclin D1蛋白在LMS和LMA中的表达率均明显高于正常平滑肌组织,而在LMS和LMA间表达率差异无显著性。原位杂交结果与免疫组化结果基本一致。结论:P16INK4A、CDK4在肉瘤发生过程中具有重要作用;cyclinD1过表达是常见的分子水平改变,且可能出现较早;检测P16INK4A、CDK4蛋白有助于鉴别子宫平滑肌肉瘤和平滑肌瘤。

Objective：To investigate the expression and value of P16^INK4A, CDK4 and cyclin D1 protein in uterine smooth muscle tumors. Methods：The expression of P16^INK4A, CDK4 and cyclin D1 protein in 21 cases of uterine leiomyosarcoma, 34 cases of uterine leiomyoma and 22 cases of normal myometrium was detected by SP immunohistochemical technique, and the expression of P16^INK4A mRNA studied by in situ hybridization. Results：Positive ratesof P16^INK4A, CDK4 and cyclin D1 in uterine leiomyosarc0ma, leiomyoma and normal myometrium were 62%, 90%, 57%; 15%, 26%, 53%; 10%, 10%, 0% respectively. There was significant difference in the expression of P16^INK4A, CDK4（P 〈 0.05） between leiomyosarcoma and leiomyoma.The expression of cyclin D1 showed significant different （P 〈 0.05） between LMS and normal myometrium, LMA and normal myometrium. The in situ hybridization result and the immunohistochemical result is basic one. Conclusion：P16^INK4A, CDK4 might play an important role in sarcomagenesis; OverexpressIon of cyclin D1 is a common molecular alteration that may occur in the early stage; Combining immunohistochemical detection of P16^INK4A and CDK4 is helpful to distinguish leiomyosarcoma from leiomyoma.