胃癌和胃癌前病变bcl-2基因表达及其对细胞凋亡的调控作用

Expression of bcl-2 gene in gastric carcinoma and precancerous lesions and its regulatory role in apoptosis

目的 探讨胃癌前病变及胃癌中bcl 2基因表达状况及其与细胞凋亡的关系。方法 应用原位杂交和免疫组织化学技术检测 10例正常胃粘膜、72例慢性萎缩性胃炎和 5 3例胃癌中bcl 2基因的表达 ,并采用凋亡细胞原位检测方法对组织切片中的凋亡细胞进行观察和比较。结果 bcl 2基因在正常胃粘膜及不同胃粘膜病变中均有不同程度的表达。bcl 2mRNA在胃癌组织中的表达率为 77 3 6%,显著高于正常胃粘膜、萎缩性胃炎及肠化生 ( 2 0 0 0 %,2 5 0 0 %,44 44 %,P<0 0 1) ;异型增生组织bcl 2mRNA表达率为 75 0 0 %,显著高于正常胃粘膜及萎缩性胃炎 (P <0 0 5 )。胃癌组织bcl 2蛋白表达率为 81 13 %,显著高于正常胃粘膜、萎缩性胃炎及肠化生 ( 2 0 0 0 %,3 1 2 5 %,5 2 78%,P <0 0 1) ,异型增生组织bcl 2蛋白表达率为 75 0 0 %,显著高于正常胃粘膜及萎缩性胃炎 (P <0 0 1)。χ2 检验表明两种方法检测阳性率差异无显著性。凋亡细胞原位检测结果显示 ,bcl 2蛋白表达阳性肠化生和胃癌组织中的凋亡细胞指数显著低于bcl 2蛋白阴性组 (P<0 0 5及P <0 0 1) ,bcl 2蛋白表达状态与细胞凋亡指数呈负相关。结论 bcl 2基因对胃癌前组织及胃癌细胞凋亡具有抑制性调控作用 。

Objective To elucidate the relationship between bcl 2 gene expression and the frequency of apoptosis in different stages of malignant transformation of gastric epithelium in precancerous lesions and gastric carcinomas. Methods In situ hybridization and immunohistochemical method were used to study the frequencies of bcl 2 gene expression in 10 cases of normal gastric mucosa, 72 cases of chronic atrophic gastritis, and 53 cases of gastric carcinoma. Meanwhile, the method of in situ apoptotic cell detection was adopted to detect the apoptotic cells in these lesions. The relationship of the number of apoptotic cells with the bcl 2 gene expression in each case was observed. Results In situ hybridization revealed that the positive frequency of bcl 2 gene expression in gastric carcinoma was significantly higher than that in normal gastric mucosa, atrophic gastritis, and intestinal metaplasia ( P <0.01 and P <0.05); and that the positive frequency of bcl 2 gene expression in gastric dysplasia was significantly higher than that in normal gastric mucosa and in atrophic gastritis ( P <0.05). The expression rate of bcl 2 protein detected by immunohistochemistry was significantly higher in gastric carcinoma than that in normal gastric mucosa, atrophic gastritis, and intestinal metaplasia ( P <0.01), and remarkably higher in gastric dysplasia than that in normal gastric mucosa and atrophic gastritis ( P <0.01). There was no significant difference between the positive rates obtained by these 2 methods. Observation of the relationship of bcl 2 expression with the number of apoptotic cells in these specimens revealed that the apoptotic index in bcl 2 positive expression group was lower than that in bcl 2 negative expression group ( P <0.01). Conclusion The expression of bcl 2 gene can inhibit apoptosis in gastric carcinoma and its precancerous lesions. The abnormal regulation of apoptosis may play an important role in the pathogenesis of gastric carcinoma.