骨肉瘤中Rb、p16、CDK_4、cyclinD_1蛋白的表达及其意义  

Significance of Rb, p16, CDK_4 and cyclinD_1 expression in osteosarcomas

作　　者：李扬[1] 丘钜世[1] 梁惠珍[1] 罗灿峤[1] 朱全胜[1] 曾瑜[2] 

机构地区：[1]中山医科大学病理教研室,广东广州510089 [2]中山医科大学第一附属医院儿科,广东广州510089

出　　处：《癌症》2000年第6期544-547,共4页Chinese Journal of Cancer

基　　金：中山医科大学"211工程"重点学科建设经费资助!(No:98028)

摘　　要：目的：探讨骨肉瘤中Ｒｂ、ｐ１６、ＣＤＫ_４、ｃｙｃｌｉｎＤ_１的蛋白表达、相互关系及其意义。方法：应用免疫组化方法对４０例骨肉瘤组织中ＲＢ、ｐ１６、ＣＤＫ_４、ｃｙｃｌｉｎＤ１的蛋白表达状况进行检测。结果：４０例骨肉瘤Ｒｂ、ｐ１６蛋白表达缺失分别为７２.５％（２９／４０）和２２.５％（９／４０）；１１例ｐＲｂ阳性的骨肉瘤中８例ｐ１６阴性，２９例ｐＲｂ阴性的骨肉瘤中２８例ｐｌ６阳性；５２.５％（２１／４０）的骨肉瘤中存在ＣＤＫ_４的过表达，１１例ｐＲｂ阳性的骨肉瘤８例ＣＤＫ_４蛋白呈过表达，３削弱阳性 ；３例 ｐＲｂ、ｐ１６均阳性的骨肉瘤 ＣＤＫ４导过表达；骨肉瘤中 ｐＲｂ， ｐ１６， ＣＤＫ_４的总异常率达１００％；４０例骨肉瘤中未检出ｃｙｃｌｉｎＤ_１蛋白的过表达。结论：（１）Ｒｂ蛋白的缺失。ＣＤＫ_４蛋白的过表达是骨肉瘤中的常见事件（２）骨肉瘤中ｐ１６与ｐＲｂ的表达呈负相关；（３）Ｒｂ蛋白阳性的骨肉瘤，ｐ１６蛋白的缺失及／或ＣＤＫ４蛋白的过表达，可能在ｐＲｂ的过度磷酸化而失活以致骨肉瘤失控地增生中起着重要作用；（４）ｐ１６－ＣＤＫ_４－ｐＲｂ通路的异常与骨肉瘤的发生密切相关。Objective: To evaluate the significance of Rb, pl6, CDK_4 and cyclinD_1 protein expression in osteosarcomas and the relationship among these proteins. Methods: A total of 40 cases of osteosarcomas were examined for pRb, pl6, CDK_4 and cyclinD_1 expression using immunohistochemistry. Results: There were 29 (72. 5% ) and 9 (22.5% ) cases lack of pRb and pl6 expression, respectively. In 11 pRb positive cases, 8 were negative for pl6. In contrast, in 29 pRb negative samples, 28 were positive for p16. CDK4 overexpression was observed in 52.5% (21/40) osteosarcoma specimens. Of the 11 pRb positive osteosarcomas, CDK_4 overexpression was appeared in 8 cases although 3 cases were faintly positive. Overexpression of CDK_4 was also observed in 3 cases of osteosarcomas which were both pRb and p16 positive. The percentage of total abnormality for pRb, pl6 and CAK_4 expression in our 40 osteosarcomas was 100%. Overexpression of cyclinD_1 was not observed in these osteosarcomas. Conclusions: (1) Loss of pRb and overexpression of CDK_4 are common molecular events in osteosarcoma. (2)There is a negative correlation between pl6 and pRb protein expression in osteosarcoma. (3)In pRb positive osteosarcomas, loss of pl6 and /or overexpression of CDK_4 may play a critical role in the hyperphosphorylation of pRb resulting in uncontrolled cell proliferation. (4)The abnormality of p16-CDK_4-pRb pathway is highly related to the pathogenesis of osteosarcoma.

关 键 词：骨肉瘤 cyclinD1 RB蛋白 P16蛋白 CDK4蛋白 

分 类 号：R738.1[医药卫生—肿瘤]