幽门螺杆菌CagA蛋白与胃癌组织中Bcl-2、p53蛋白表达的关系  

Relationship between expression of Bcl-2 and p53 protein and CagA+ Helicobacter pylori in gastric cancer

作　　者：杜雅菊[1] 赵晶[1] 赵瑞波 李宝杰[1] 

机构地区：[1]哈尔滨医科大学附属第二临床医学院消化内科,黑龙江省哈尔滨市150086 [2]哈尔滨医科大学基础医学院病理教研室,黑龙江省哈尔滨市150086

出　　处：《世界华人消化杂志》2003年第5期554-557,共4页World Chinese Journal of Digestology

摘　　要：目的:CagA+H.pylori感染与胃癌的相关性在我国报道不一,且致癌机制不祥.本研究应用ELISA法检测H.pylori相关胃癌和慢性胃病血清中抗CagA抗体和免疫组化方法检测全部组织标本中Bcl-2、p53蛋白的表达,研究H.pyloriCagA阳性株感染与胃癌、慢性胃病的相关性及与胃黏膜组织中Bcl-2、p53蛋白表达的相互关系,探讨H.pylori的致癌机制.方法:79例患者(胃癌50例、萎缩性胃炎17例、胃溃疡伴不典型增生5例、浅表性胃炎7例)胃镜诊断明确后取胃窦或病变部位活检,用于H.pylori的诊断、病理诊断及免疫组化检测Bcl-2、p53蛋白的表达.H.pylori的诊断采用快速尿素酶试验和ELISA法血清H.pylori抗体或病理Warthin-Starry银染色,两项阳性诊断为H.pylori阳性.用ELISA法检测患者血清CagA-H.pylori抗体,用免疫组化方法检测全部组织标本中Bcl-2、p53蛋白的表达.结果:胃癌组CagA+H.pylori感染阳性率86%(43/50)高于慢性胃病组45%(13/29)(P<0.01),有显著性差异.Bcl-2蛋白表达:胃癌组高于慢性胃病组(62%vs41%;P>0.05),胃癌CagA+组高于CagA-组(65%vs43%;P>0.05),慢性胃病CagA+组显著高于CagA-组(77%vs12%;P<0.01).p53蛋白表达:胃癌组显著高于慢性胃病组(54%vs28%;P<0.05),胃癌CagA+组显著高于CagA-组(60%vs14%;P<0.05),慢性胃病CagA+组显著高于CagA-组(46%vs12%;P<0.05).结论:胃癌患者CagA+H.pylori感染明显高于慢性胃病者,CagA+H.pylori感染与胃癌发生明显相关,而H.pylori的CagA可使癌前疾病组织中出现Bcl-2蛋白表达,且随着Bcl-2蛋白表达增加疾病的严重程度也增加,即在细胞恶性转化的早期阶段就发挥作用,并逐渐增强,导致胃上皮细胞增生增加,凋亡减少.增生的过程中继而出现p53基因的突变,即突变型p53蛋白表达增强,诱导凋亡作用减弱.AIM:The relationship between cytotoxin-associated protein (CagA)+Helicobacter pylori (H.pylori) infection and gastric cancer in China was reported inconsistently. Using enzyme-linked immunosorbent assay (ELISA) to detect serum anti-CagA antibody and ABC immunohistochemical staining to detect the expression of Bcl-2 and p53 proteins, this study is to explore the relationship between CagA H.pylori infection and expressions of p53 and Bcl-2 proteins in gastric cancer and chronic gastric diseases. METHODS:Seventy-nine patients (50 with gastric cancer, 17 with chronic atrophic gastritis, 5 with gastric ulcer and 7 with chronic superficial gastritis) were diagnosed by endos- copy and biopsied under endoscopy for detection of H.pylori infection, and confirmed by pathological examination. Expression of Bcl-2 and p53 proteins was detected by immunohistoche- mistry. Rapid urease test and serum H.pylori antibodies with ELISA or Warthin-Starry silver stains were used for H.pylori diagnosis. H.pylori was defined as positive when 2 or 3 of these tests were positive. ELISA was used for the detection of serum anti-CagA antibody. RESULTS:Anti-CagA antibody was present in 43/50 (86 %) gastric cancer and in 13/29 (41 %) chronic gastric disease, CagA+ H.pylori rate in gastric cancer was higher than those in chronic gastric diseases (P <0.01). The positive rate of Bcl-2 expression in gastric cancer was higher than that inchronic gastric diseases (62 % vs 41 %, P >0.05). In CagA+ gastric cancer it was higher than that in CagA- one (65 % vs 43 %, P >0.05), and in CagA+ chronic gastric diseases it was higher than that in CagA- one (77 % vs 12 %, P <0.01). The positive rate of mutant p53 expression in gastric cancer was higher than that in chronic gastric diseases (54 % vs 28 %, P <0.05), in CagA+ gastric cancer it was significantly higher than that in CagA- one (60 % vs 14 %, P <0.05), and in CagA+ chronic gastric diseases it was significantly higher than that in CagA- ones (46 % vs 12 %, P <0.05). CONCLUSION:Expression of anti-CagA ant

关 键 词：幽门螺杆菌 CAGA蛋白 胃癌 BCL-2蛋白 P53蛋白 ELISA法 作用机制 细胞增生 

分 类 号：R735.2[医药卫生—肿瘤] R378.99[医药卫生—临床医学]