大肠肿瘤p53蛋白过表达对原位Th1/Th2平衡的影响

Effects of p53 overexpression on the balance of helper T cell 1 with helper T cell 2 in colorectal tumors

目的 :评价 p5 3蛋白过表达对大肠腺瘤和大肠癌局部辅助T细胞 (Th1 Th2 )平衡的影响 ,进而探讨大肠癌发生的免疫学机制。方法 :研究对象包括大肠腺瘤 30例、大肠癌 38例 ,癌旁正常粘膜 6 8例作为对照组。石蜡切片以免疫组化法检测 p5 3蛋白表达 ,采用酶联免疫吸附试验 (ELISA)检测肠组织培养上清液中 4种细胞因子(IL 2 ,IL 4 ,IL 10 ,IFN r)水平。结果 :p5 3蛋白表达阳性组培养上清液的IL 2、IFN r水平显著低于阴性组和对照组 (P <0 .0 1) ,而IL 10则高于阴性组及对照组 (P <0 .0 5 ) ,各组IL 4水平未显示差异 (P >0 .0 5 )。结论 :p5 3蛋白表达引起原位Th1 Th2平衡失调 ,表现为由Th1向Th2漂移。初步推断 :p5 3基因失活在大肠癌发生的免疫学机制中可能具有重要作用。

Purpose:To evaluate the effects of p53 overexpression on the balance of in situ T helper cell 1 with T helper cell 2 in colorectal adenomas and carcinomas, with further study of the immunological mechanism of p53 overexpression stimulating colorectal cancer formation.Methods:Endoscopic colorectal mucosal biopsies were taken from 68 patients with colorectal tumors,including adenomas(n=30) and carcinomas(n=38),and their normal mucosas served as control(NS,n=68).Paraffin sections were examined immunohistochemically for p53 protein overexpression and four cytocine(IL-2,IL-4,IL-10,IFN-r) levels were detected by enzyme linked immunosorbent assay(ELISA) with the culture supernatants of colorectal tissue.Results:IL-2 and IFN-r levels in culture supernants of the positive group were significantly lower (P<0.01),in contrast,IL-10 levels were significantly higher (P<0.05) than those of the negative group,but there was no difference of IL-4 levels among all groups(P>0.05).Conclusions:p53 overexpression induced inbalance of in situ Th1 with Th2 levels,shown as a drift from Th1 toTh2.p53 gene inactivation may play an critical role in immunological mechanism of colorectal carcinoma carcinogenesis.