人脑星形细胞瘤P^(21WAF1)/CIP1的表达与P^(53)、MDM2及细胞增殖指数间的关系  

Expression of P^(21 WAF1)/CIP1 in Human Astrocytomas in Correlating with P^(53), MDM2, and Cellular Proliferation Index

作　　者：徐庆中[1] 刘芳[1] 卢德宏[1] 于士柱[1] 杨虹[1] 

机构地区：[1]首都医科大学宣武医院病理科,北京100053

出　　处：《中国医学科学院学报》2001年第4期340-345,共6页Acta Academiae Medicinae Sinicae

摘　　要：目的 探讨P^(21)、P^(53)和MDM2表达与人脑星形细胞瘤发生、发展及与细胞增殖指数间的关系。方法 用免疫组化技术检查41例石蜡包埋的人脑星形细胞瘤标本P^(21)、P^(53)和MDM2蛋白的表达和由增殖细胞核抗原（PCNA）反映的细胞增殖程度，同时用RNA原位杂交技术检测24例新鲜人脑星形细胞瘤标本的p21 mRNA表达情况。结果p21 mRNA原位杂交检查中无论是高级别肿瘤组或低级别肿瘤组，表达均有明显的差异。免疫组化检查中P^(21)、P^(53)、 MDM2和PCNA的阳性率分别为75．6%、68．3%、65．9%和100%。P21蛋白表达在高级别肿瘤中较高(P ＝ 0．001)，且与细胞增殖指数明显相关，但与P^(53)表达和MDM2表达无明显相关。P^(53)表达与肿瘤组织学分级无关(P ＝0．424)，但与细胞增殖指数明显相关。MDM2表达与肿瘤组织学分级无关(P ＝ 0．812)，与细胞增殖指数亦无明显相关性。多元线性逐步回归分析表明，细胞增殖指数(PCNALI)和P21标记指数与肿瘤组织学分级有密切关系(P ＝ 0．000和P ＝ 0．001)。结论 （1）p21 mRNA和P21蛋白在人脑星形细胞瘤中过度表达,其与细胞增殖指数相关,但与P^(53)表达无关,表明可能有不依赖于P^(53)的通路诱导P^(21)表达。仅有P^(21)过度表达对抑制肿瘤生长是不够的,还需要PCNA参与；（2）P^(53)?Objective To study the correlation between the expression of p21, p53, MDM2 gene products and the initiation and progression of human astrocytomas． Methods The expression of P21, P53, MDM2,and proliferative cell nuclear antigen(PCNA) labeling index using immunohistochemistry in 41 paraffin embedded human astrocytoma samples． As well as the expression of p21 mRNA using mRNA in situ hybridization in 24 fresh human astrocytoma samples stored at －70℃ were investigated． In immunohist- ochemistry, we divided whole tumor cells by positive tumor cell nuclei to obtainlabeling index(LI), in this way we could understand the protein product expression of gene in astrocytoma in different patients． In mRNA in situ hybridization, the expression of p21 mRNA was scored according to the rough percentage of positive cells． Results In p21 mRNA in situ hybridization, the positive staining was present in 87．5%． In immunohistochemistry, positive P^(21), P^(53), MDM2, and PCNA staining were presented in 75．6%, 68．3%, 65．9%, 100% respectively． Higher levels of P^(21) protein expression were seen in higher histological grade(P ＝ 0．001)． The association between P^(21) expression positively correlated with proliferation index． But not with P^(53) expression and MDM2 expression． The association between P^(53) expression and proliferation indices were statistically significant, but the expression of P^(53) was not related to tumor grade． There was no association between MDM2 expression and grade, or cellular proliferation index． Linear stepwise regression analysis showed the parameters affecting tumor grade were PCNA LI(P ＝ 0．000)and P^(21) LI(P ＝ 0．001)． Conclusions (1)Both p21 mRNA and P^(21) protein were overexpressed in human astrocytomas, the overexpression was related to cellular prolifera- tion index, but was not related to P^(53) expresssion, suggesting there could be P^(53)-independent pathway to induce the P^(21) expression, in additon, the overexpression of P^(21) alone appeared

关 键 词：星形细胞瘤 P^21WAF1/CIP1 P^53 MDM2 增殖细胞核抗原 原位杂交 脑肿瘤 

分 类 号：R739.410.2[医药卫生—肿瘤] R730.264[医药卫生—临床医学]