大肠肿瘤的基因表达及与细胞凋亡的抑制关系

目的探讨 bcl-2和 P53蛋白在大肠肿瘤中的表达及与细胞凋亡关系。方法用免疫组化方法观察了45例大肠腺瘤和61例大肠癌中 bcl-2和 P53蛋白的表达。结果正常大肠粘膜中 bcl-2和 p53均未见表达,而大肠腺瘤及大肠癌阳性率均较正常明显增加(P<0.01)。大肠腺瘤 p53表达随腺瘤大小增加而增加,其中≥20 mm 组阳性率(77.8%)显著高于<10 mm 组(35.0%,P<0.05)。P53蛋白阳性率也随不典型增生程度增加而增高。p53表达与大肠癌分化程度及 Duke 分期有关。大肠癌细胞凋亡指数与 bcl-2阳性表达呈负相关。大肠腺瘤中 bcl-2和 P53蛋白的表达也呈负相关。结论 bcl-2蛋白表达对大肠癌前病变.腺瘤的增殖有一定意义,p53在大肠腺瘤癌变和大肠癌进展中起重要作用,它们是参与细胞凋亡的良好指标。

Oncoprotein expression and inhibition of apoptosis during colorectal tumorigenesis

AIM: To study bcl-2 and p53 protein expression and inhibition of apoptosis during colorectal tumorigenesis. METHODS: Expression of bcl-2 and p53 was detected by immunohistochemical staining of 45 colorectal adenomas, 61 colorectal carcinomas, and 15 pathologically-confirmed normal colorectal biopsies. RESULTS: The bcl-2 and p53 protein expression was uniformly negative in the normal mucosa specimens, whereas bcl-2 and p53 positive rates were significantly higher in the adenoma and carcinoma specimens (P < 0.01). Strong bcl-2 expression was often present in areas of severe dysplasia. In the colorectal adenoma specimens, expression of p53 increased with increasing size and dysplasia, being higher in adenomas ≥ 20 mm in diameter than in adenomas < 10 mm in diameter (77.8% vs 35.0%, P < 0.05). p53 protein expression was correlated with differentiation and Duke's staging. A significant inverse correlation was found between immunostaining of bcl-2 and p53 in adenomas but not in carcinomas. Furthermore, carcinomas with a high percentage of bcl-2 positive cells were significantly more likely to have low rates of apoptosis. CONCLUSION: Bcl-2 expression appears to be an early event in colorectal tumorigenesis that can inhibit apoptosis. p53 expression plays an important role in the development and malignant change of colorectal adenoma. Bcl-2 and p53 may represent useful markers of cell apoptosis.