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。

Expression and significance of CDK4,p18,p19 in canceration of esophageal epithelium

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.