细胞周期相关蛋白cyclin D1、p53和p21^(WAF1/Cip1)在食管鳞癌中的表达改变及其病理学意义  

Expression of cell cycle related proteins cyclin D1,p53 and p21^(WAF1/Cip1) in esophageal squamous cell carcinoma

作　　者：林德晨[1] 史志周[1] 薛丽燕[2] 陈微[1] 徐昕[1] 韩亚玲[1] 吕宁[2] 王明荣[1] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所分子肿瘤学国家重点实验室,北京100021 [2]中国医学科学院北京协和医学院肿瘤医院病理科,北京100021

出　　处：《遗传》2010年第5期455-460,共6页Hereditas（Beijing)

基　　金：国家科技支撑计划(编号:2006BAI02A14);863计划重大专项(编号:2006AA02A403)资助

摘　　要：食管鳞状细胞癌(Esophageal squam ous cell carcinom a,ESCC)是我国常见的恶性肿瘤之一,虽然临床诊治手段正逐步改进,但中晚期患者5年生存率仍然很低。目前认为细胞周期调控异常与肿瘤发生发展关系密切,然而相关周期调节蛋白在食管癌患者中的表达改变、临床意义及其应用价值还没有明确结论。文章应用组织微阵列联合免疫组织化学技术(TMA-IHC),对148例食管鳞癌组织标本中细胞G1/S期调控蛋白cyclinD1、p53和p21WAF1/Cip1的表达进行检测,分析其与临床病理参数之间的相关性。结果显示,cyclinD1与p53蛋白在食管癌细胞中表达升高,p53表达阳性率与区域淋巴结转移显著相关(P=0.001)。p21WAF1/Cip1蛋白在肿瘤组织中表达降低,且p21WAF1/Cip1表达阴性患者的术后生存时间显著短于表达阳性的患者(P=0.001)。多因素生存分析显示p21WAF1/Cip1是一个独立的预后因素(相对危险度为0.418,P<0.001)。微阵列比较基因组杂交(array-CGH)检测进一步表明45.4%的食管癌患者存在cyclinD1基因扩增。以上结果提示食管鳞癌中存在细胞周期G1/S期调控异常,p21WAF1/Cip1蛋白可能是一个有应用价值的预后因子。Dysregulation of cell cycle control,especially G1/S phase transition,is implicated in the pathogenesis of most human cancers,including esophageal squamous cell carcinoma（ESCC）.However,the clinicopathological significance of aberrant expression of G1/S phase-related proteins in ESCC remains unclear.In the present study,cyclin D1,p21WAF1/Cip1 and p53 protein expression were examined in 148 ESCC cases using immunohistochemistry combined with tissue microarray.We then analyzed the correlations between their expression and clinicopathological parameters and found that overexpression of p53 was associated with lymph node metastasis（P=0.001）.p21WAF1/Cip1 down-regulation was an independent prognostic factor by multivariate analysis（RR=0.418,P0.001）.Further more,array-CGH results revealed that cyclin D1 gene was amplified in 45.4% of ESCC patients.This study confirms that dysregulation of G1/S related genes is common in ESCC and reduced expression of p21WAF1/Cip1 protein can predict shorter overall survival time of patients with ESCC.

关 键 词：食管鳞状细胞癌 细胞周期 免疫组化 组织微阵列 预后判断 

分 类 号：R735.1[医药卫生—肿瘤]