表皮生长因子受体、人类表皮生长因子2、拓扑异构酶Ⅱ在食管上皮癌变过程中的表达及意义

 【摘要】　目的　探讨表皮生长因子受体（EGFR）,人类表皮生长因子2（Her-2）,拓扑异构酶Ⅱ（TOPOⅡ）在食管上皮癌变过程中的蛋白表达情况与临床病理参数的关系以及三者之间的相互关系。方法　收集107例食管鳞状细胞癌标本,均包括食管正常上皮、上皮内瘤变和鳞状细胞癌。应用组织芯片技术和免疫组织化学EnVision二步法分析EGFR、Her-2、TOPOⅡ的蛋白表达。 结果　从食管正常鳞状上皮、低级别上皮内瘤变、高级别上皮内瘤变到癌的发展过程中EGFR与TOPOⅡ表达率呈现逐步上升的趋势（8.41 %、7.94 %、27.27 %、50.47 %;3.74 %、4.76 %、20.45 %、43.93 %）（P＝0.031）。且随着组织学分级的增加二者的表达水平递增（P＝0.009）,但与性别、年龄、浸润深度、淋巴结转移情况无相关关系。Spearman相关分析显示其二者的表达呈正相关（ r 1＝0.410,P＜0.05）。Her-2蛋白表达在3组之间差异无统计学意义（P＞0.05）,与各病理学参数比较差异亦无统计学意义（P＞0.05）,且与EGFR、TOPOⅡ蛋白表达无相关性（r 2＝0.112,P＞0.05;r 3＝0.186,P＞0.05）。结论　EGFR、TOPOⅡ与食管鳞状细胞癌发生、发展密切相关,尤其在高级别上皮内瘤变阶段其蛋白表达发生质的改变。而Her-2基因在山西地区食管癌发生、发展中作用尚不确定。     

食管上皮癌变过程中CDK4、p18、p19的表达及意义

 【摘要】　目的　探讨细胞周期调控蛋白CDK4、p18、p19在食管鳞状细胞癌（SCC）发生、发展中的作用。方法　制作组织芯片,用免疫组织化学EnVision二步法对120例食管癌患者手术标本中CDK4、p18、p19的表达进行检测,并对其结果进行统计分析。结果　CDK4蛋白在正常食管上皮的表达低[28.3 %（34／120）],瘤变上皮中有所增高[32.5 %（39／120）],食管SCC中表达高[84.2 %（101／120）],且随SCC分化程度的降低而逐渐增高,SCC与正常上皮及瘤变上皮中CDK4表达阳性率差异有统计学意义（χ2＝76.004,P＜0.05;χ2＝65.897,P＜0.05）。淋巴结转移组CDK4表达率[93.88 %（46／49）]高于无淋巴结转移组[71.43 %（55／71）]（χ2＝5.860,P＜0.05）。p18、p19 蛋白在正常食管上皮组织阳性表达率分别为34.2 %（41／120）、29.2 %（35／120）,在食管瘤变上皮中表达率分别为19.2 %（23／120）、15.0 %（18／120）,在SCC中表达率分别为63.3 %（76／120）、61.7 %（74／120）,两指标在正常上皮及瘤变上皮间、瘤变上皮与SCC间、正常上皮与SCC间差异均有统计学意义（p18：χ2＝6.903、48.296、20.429,均P＜0.05;p19：χ2＝6.998、55.276、25.565,均P＜0.05）;在食管SCC中随分化程度的降低而逐渐增高。p18、p19分别与CDK4基因表达呈正相关（r＝0.696、0.630,均P＜0.05）。p18与p19二者呈正相关（r＝0.833,P＜0.05）。结论　细胞周期调控基因CDK4 、p18、p19参与食管SCC的发生、发展,其蛋白表达与食管上皮癌变密切相关。     

食管上皮癌变过程中CDK4、p18、p19的表达及意义

Objective To investigate the role of cell cycle regulatory protein CDK4,p18,p19 in the genesis and development of esophageal squamous cell carcinoma (SCC).Methods Tissue microarray and immunohistochemical method (Envision) were used to detect the protein expression of CDK4,p18,p19 in 120 cases of esophageal tissues.The results were statistically analyzed.Results The positive rate of CDK4 protein expression in normal esophageal epithelium was low [28.3 % (34/120)],it increased in esophageal intraepithelial neoplasia [32.5 % (39/120)],and it was high in esophageal SCC [84.2 % (101/120)],which increased with the degree of SCC differentiation decreasing gradually.There was significant differences between the SCC and normal esophageal epithelium or esophageal intraepithelial neoplasia (x2= 76.004,P ＜0.05; x 2= 65.897,P ＜ 0.05).The expression of CDK4 in group with lymphatic metastasis [93.88 % (46/49)]was higher than without it [71.43 % (55/71)] (x2= 5.860,P ＜ 0.05).The positive rates of p18,p19 protein expression in normal esophageal epithelium were high [34.2 % (41/120),29.2 % (35/120)],it decreased in esophageal intraepithelial neoplasia [19.2 % (23/120),15.0 % (1 8/120)] (x 2= 134.481,P ＜ 0.05; x 2 = 141.376,P ＜ 0.05),but it were high in esophageal SCC [63.3 % (76/120) and 61.7 % (74/120)] which decreased with the degree of SCC differentiation gradually increased.There were significant differences between the normal esophageal epithelium and esophageal intraepithelial neoplasia,esophegeal intraepithelial neoplasia and SCC,normal esophageal epithelium and SCC (p 18:x 2 = 6.903,48.296,20.429,P ＜ 0.05; p1 9:x2 = 6.998,55.276,25.565,P＜ 0.05).CDK4 protein expression was correlated with both p18 and p19 (r =0.696,0.630,P ＜0.05),and there was significant positive correlation between the protein expression of p18 and p19 (r =0.833,P ＜0.05).Conclusion Cell cycle regulatory gene CDK4,p18,p19 get involved in the genesis and development of esophageal squamous cell carcinoma.Their protein expressions are closely related to canceration of esophageal epithelium.     

食管上皮癌变过程中CDK4、p18、p19的表达及意义

Objective To investigate the role of cell cycle regulatory protein CDK4,p18,p19 in the genesis and development of esophageal squamous cell carcinoma (SCC).Methods Tissue microarray and immunohistochemical method (Envision) were used to detect the protein expression of CDK4,p18,p19 in 120 cases of esophageal tissues.The results were statistically analyzed.Results The positive rate of CDK4 protein expression in normal esophageal epithelium was low [28.3 % (34/120)],it increased in esophageal intraepithelial neoplasia [32.5 % (39/120)],and it was high in esophageal SCC [84.2 % (101/120)],which increased with the degree of SCC differentiation decreasing gradually.There was significant differences between the SCC and normal esophageal epithelium or esophageal intraepithelial neoplasia (x2= 76.004,P ＜0.05; x 2= 65.897,P ＜ 0.05).The expression of CDK4 in group with lymphatic metastasis [93.88 % (46/49)]was higher than without it [71.43 % (55/71)] (x2= 5.860,P ＜ 0.05).The positive rates of p18,p19 protein expression in normal esophageal epithelium were high [34.2 % (41/120),29.2 % (35/120)],it decreased in esophageal intraepithelial neoplasia [19.2 % (23/120),15.0 % (1 8/120)] (x 2= 134.481,P ＜ 0.05; x 2 = 141.376,P ＜ 0.05),but it were high in esophageal SCC [63.3 % (76/120) and 61.7 % (74/120)] which decreased with the degree of SCC differentiation gradually increased.There were significant differences between the normal esophageal epithelium and esophageal intraepithelial neoplasia,esophegeal intraepithelial neoplasia and SCC,normal esophageal epithelium and SCC (p 18:x 2 = 6.903,48.296,20.429,P ＜ 0.05; p1 9:x2 = 6.998,55.276,25.565,P＜ 0.05).CDK4 protein expression was correlated with both p18 and p19 (r =0.696,0.630,P ＜0.05),and there was significant positive correlation between the protein expression of p18 and p19 (r =0.833,P ＜0.05).Conclusion Cell cycle regulatory gene CDK4,p18,p19 get involved in the genesis and development of esophageal squamous cell carcinoma.Their protein expressions are closely related to canceration of esophageal epithelium.