甲状腺癌p53调节基因Mdm2以及p21^(WAF/CIP1)蛋白的表达  

Expression of proteins in p53(Mdm2-p53-p21^(WAF/CIP1)) pathway in thyroid carcinoma

作　　者：彭树文[1] 黄健男[1] 季锡清[2] 盛新华[2] 唐井岗[2] 张银喜 

机构地区：[1]广东省第二人民医院耳鼻咽喉头颈外科,广东广州510317 [2]第一军医大学南方医院普外科,广东广州510515 [3]解放军第二八五医院普外科,河北邯郸056000

出　　处：《中国耳鼻咽喉头颈外科》2006年第6期372-376,共5页Chinese Archives of Otolaryngology-Head and Neck Surgery

摘　　要：目的探讨p53、鼠双微体2(murinedonbleminute2,Mdm2)及p21WAF/CIP1等蛋白在甲状腺癌组织中的表达、意义及相互作用关系。方法取甲状腺癌、癌旁与良性病变组织构建组织芯片,应用免疫组化方法检测p53、Mdm2及p21WAF/CIP1在甲状腺良恶性病变中的表达。结果p53、Mdm2及p21WAF/CIP1在甲状腺癌中表达的阳性率分别为50.6%(37/73),63.0%(47/73)和38.4%(28/73)。同癌旁组织相比,p53和Mdm2表达明显升高(P<0.01),而p21WAF/CIP1的表达明显降低(P<0.05)。p21WAF/CIP1和p53的阳性表达均与未分化癌、有无淋巴结转移及受累程度显著相关(P<0.05);Mdm2的阳性表达与甲状腺良恶性病变显著相关(P<0.05)。三者阳性表达两两之间统计学上具有关联性(P<0.05)。结论p53和Mdm2的过表达以及p21WAF/CIP1的缺失表达可能会导致甲状腺癌的恶性形成和进展;三者中蛋白主要以p53-Mdm2-p21WAF/CIP1通路的方式作用于细胞的转化和肿瘤的形成;联合检测p53和Mdm2的表达可用于评定甲状腺癌的恶性程度。检测p21WAF/CIP在甲状腺癌中表达的变化可用于评估其生物学行为和判断预后。OBJECTIVE To investigate the significance of expression of p53, Mdm2 and p21^WAF/CIP1 proteins and their relationships. METHODS Pathological specimens from thyroid carcinoma, adjacent non-tumor thyroid tissues and thyroid benign lesions were examined for p53, Mdm2 and p21^WAF/CIP1 proteins by tissue microarray technique and immunohistochemistry method. RESULTS The positive expression rate of p53, Mdm2 and p21^WAF/CIP1 in thyroid carcinoma was 50.6 %（37/73）, 63.0 %（47/73） and 38.4 %（28173） respectively. The expression of p53 and Mdm2 increased（P〈0.01）, while the expression of p21^WAF/CIP1 decreased （P〈0.05） in thyroid carcinoma compared with that in non-tumor tissues. The p21^WAF/CIP1 and p53 expression in thyroid carcinoma were significantly correlated with undifferentiated carcinomas, positive lymph node metastasis or stage Ⅲ, Ⅳ tumors （P〈0.05）. Mdm2 expression was highly associated with tumor differentiation （P〈0.05）. There were statistic correlations among these three genes （P〈0.05）. CONCLUSION Overexpression of p53 and Mdm2 and loss of p21^WAF/CIP1 expression may contribute to the formation and development of thyroid carcinoma. Three proteins may play a critical role in cell cycle arrest and apoptosis after DNA damage through the so-called MDM2-p53-p21^WAF/CIP1 pathway. Co-detection of the overexpression of p53 and Mdm2 can be used to evaluate the differentiation and prognosis of thyroid carcinoma. Examination of expression of p21^WAF/CIP1 proteins may be helpful to judge the biological behavior and prognosis of thyroid cancer.

关 键 词：甲状腺肿瘤 芯片分析技术 癌基因蛋白质 蛋白质P53 

分 类 号：R736.1[医药卫生—肿瘤]