大肠癌和腺瘤中的细胞凋亡及其调控基因表达

目的通过观察结、直肠腺癌和腺瘤中的细胞凋亡及其调控基因ｐ５３、ｂｃｌ－２的表达状态，探讨细胞凋亡及其调控基因在大肠上皮恶性转化进程的不同阶段中的作用。方法利用ＤＮＡ缺口末端标记技术和ｐ５３、ｂｃｌ－２蛋白免疫组化染色，原位观察３２例大肠绒毛状腺瘤和３３例大肠乳头状腺癌中的凋亡细胞和ｐ５３、ｂｃｌ－２蛋白阳性表达细胞的密度与分布，以１５例非肿瘤大肠粘膜做为对照。结果腺瘤和腺癌中的凋亡细胞密度均显著高于非肿瘤粘膜（Ｐ＜０．０１）；腺瘤高于腺癌（Ｐ＜０．０１）。ｐ５３和ｂｃｌ－２蛋白的表达率和表达强度，腺癌和腺瘤高于非肿瘤粘膜（Ｐ＜０．０１），腺癌的表达强度也高于腺瘤（Ｐ＜０．０５）。腺瘤中ｂｃｌ－２蛋白表达阳性组的凋亡细胞密度显著低于ｂｃｌ－２阴性组（Ｐ＜０．０１）。结论细胞凋亡调控异常在大肠癌发病中可能起重要作用。ｂｃｌ－２蛋白在腺瘤和腺癌中均可抑制细胞凋亡，而突变型ｐ５３蛋白可能仅在腺癌中起抑制细胞凋亡的作用。

Apoptosis and expression of its regulating genes in adenoma and adenocarcinoma of large intestine

Objective To investigate the effects of apoptosis and its regulating genes in different stages of malignant transformation of large instestine epithelium in colorectal adenoma and adenocarinoma.Methods The density and distribution of the apoptotic cells and the positive expression of p53 and bcl 2 oncoprotein were observed in situ in 32 villous adenomas and 33 papillary adenocarinomas of the large intestine,using DNA nick end labelling technique and immunohistochemical staining for p53 and bcl 2 oncoprotein.15 nontumor mucosa were used as controls.Results The density of apoptotic cells in adenoma and adenocarcinoma was significantly higher than that in nontumor mucosa( P <0 01),and their density in adenoma was higher than in adenocarcinoma( P <0.01).The positive rate and staining intensity of p53 and bcl 2 oncoprotein in adenoma and adenocarcinoma were significantly higher than in non tumor mucosa( P <0.01),their staining intensity in adenocarcinoma was higher than that in adenoma( P <0.01).In adenoma,the density of apoptotic cells in the bcl 2 oncoprotein positive group was higher than that in the bcl 2 oncoprotein negative group( P <0.01).Conclusion The abnormal regulation of apoptosis may play an important role in the pathogenesis of large intestine carcinoma.The bcl 2 oncoprotein can inhibit apoptosis in adenoma and adenocarcinoma.However,mutational p53 oncoprotein may likely block apoptosis in adenocarcinoma