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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 investigate the protein expression, relationship and significance of Rb, p16, CDK_4 and cyclinD_1 in osteosarcoma. Methods: Immunohistochemistry was used to detect the expression of RB, p16, CDK4 and cyclinD1 in 40 cases of osteosarcoma. Results: The loss of Rb and p16 protein expression in 40 cases of osteosarcoma was 72.5% (29/40) and 22.5% (9/40) respectively; in 11 cases of pRb positive osteosarcoma, 8 cases were p16 negative and 29 cases were pRb. Positive pl6 was found in 28 cases of negative osteosarcoma; overexpression of CDK4 was found in 52.5% (21/40) osteosarcoma; CDK4 protein was overexpressed in 8 cases of pRb-positive osteosarcoma; 3 was positive in 3 cases; CDK4 was overexpressed in osteosarcoma with positive pRb and p16 expressions. The total abnormal rate of pRb, p16 and CDK4 in osteosarcoma was 100%. No overexpression of cyclinD_1 protein was detected in 40 osteosarcomas. Conclusion: (1) The deletion of Rb protein. The overexpression of CDK4 protein is a common event in osteosarcoma. (2) The expression of p16 and pRb in osteosarcoma is negatively correlated; (3) The Rb protein is positive in osteosarcoma, the loss of p16 protein and/or the overexpression of CDK4 protein. It may play an important role in inactivation of pRb due to hyperphosphorylation and uncontrolled proliferation of osteosarcoma. (4) Abnormalities of p16-CDK4-pRb pathway are closely related to the occurrence of osteosarcoma.