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目的:探讨p16蛋白与人脑星形细胞瘤生物学行为的相关性。方法:采用免疫组织化学技术检测62例星形细胞瘤标本中p16、Rb、cyclinD1基因产物及Ki-67抗原的表达情况,探讨P16-cyclinDl/CDK4-pRb细胞周期调控通路的调控机制和p16蛋白与星形细胞瘤生物学行为的相关性。结果:(1)星形细胞瘤中pl6-cyclinD1/CDK4-pRb细胞周期调控通路存在异常调节和表达,以单个异常为主,占64.52%(40/62)。(2)p16蛋白表达缺失率为43、55%(27/62),恶性组(WHOⅢ-Ⅳ级)为65.63%(21/32),随病理分级的增高,缺失率增加(P<0.001);p16蛋白表达缺失者有较高的增殖标记指数(r=-026,P<0.05);p16蛋白表达与KPS评分呈正相关(r=0.44,P<0.001)。结论:p16、Rb、cyclinD1基因产物的异常表达和调节,尤其是p16蛋白缺失与星形细胞瘤发生发展密切相关,是反映星形细胞瘤恶性生物学行为的重要分子标志物之一。
Objective: To investigate the correlation between p16 protein and biological behavior of human astrocytomas. METHODS: Immunohistochemistry was used to detect the expression of p16, Rb, cyclinD1 gene and Ki-67 antigen in 62 specimens of astrocytomas. The regulatory mechanism of p16-cyclinDl/CDK4-pRb cell cycle regulatory pathway and p16 protein were explored. Correlation with the biological behavior of astrocytoma. RESULTS: (1) The aberrant regulation and expression of pl6-cyclinD1/CDK4-pRb cell cycle pathway in astrocytomas were observed. The single abnormality accounted for 64.52% (40/62). (2) The deletion rate of p16 protein was 43 and 55% (27/62). The malignant group (WHO III-IV) was 65.63% (21/32). With the increase of pathological grade, the deletion rate increased (P<0. 001); p16 protein expression loss was higher in the proliferation index (r = -026, P <0.05); p16 protein expression was positively correlated with the KPS score (r = 0.44, P <0.001). Conclusion: Abnormal expression and regulation of p16, Rb and cyclinD1 gene products, especially p16 protein deletion, are closely related to the development of astrocytoma. It is one of the important molecular markers reflecting the malignant biological behavior of astrocytoma.