幽门螺杆菌与蛋白激酶C在胃癌及癌前病变基因突变中的作用  

Effects of Helicobacter pylori and protein kinase C on gene mutation in gastric cancer and precancerous lesions

作　　者：陈世耀[1] 王吉耀[1] 纪元[1] 张希德[1] 朱畴文[1] 

机构地区：[1]复旦大学医学院附属中山医院消化科,上海市200032

出　　处：《世界华人消化杂志》2001年第3期302-307,共6页World Chinese Journal of Digestology

基　　金：GMB基金;No.96-628

摘　　要：目的通过检测慢性胃炎、肠化生、不典型增生和胃癌组织中幽门螺杆菌(Hp)感染、蛋白激酶C(PKC)水平、细胞增殖水平以及p53突变基因表达状态探讨Hp感染在胃癌发生中的作用及其作用机制。方法采用病例对照研究,病例来源于中山医院,经内镜和病理检查证实。Hp感染采用快速尿素酶和病理Gimsa染色检测。PKC的检测采用免疫组化EnVision^(TM)法,增殖细胞核抗原(PCNA)、突变型p53基因表达的检测采用免疫组织化学方法。结果①总的Hp感染的检出率为76.2％(138/181)。在慢性胃炎肠化生组、不典型增生组、胃癌组分别为62.0％(31/50),88.6％(39/44),78.3％(68/87),均明显高于单纯慢性胃炎对照组52.6％(20/38,P<0.05)。②PCNA增殖指数在三组病例中均处于高水平,且Hp阳性组均高于Hp阴性组。③突变型p53基因表达在肠上皮化生、不典型增生和胃癌组阳性率分别为36.0％(18/50),54.6％(24/44),57.2％(48/84)。不典型增生和胃癌组均明显高于肠上皮化生组。在肠化生组,Hp阳性病例的P53表达率明显高于Hp阴性病例(48.5％ vs15.8％,P=0.020)。但在不典型增生和胃癌组,Hp阳性与Hp阴性病例的P53突变蛋白表达率无明显差别(53.9％ vs60.0％,P=0.794;53.8％ vs 68.4％,P=0.258)。P53表达与PCNA增殖指数有明显的相关性。④PKC在慢性胃炎伴肠化生、不典型增生和胃癌组阳性表达的比例呈递增趋势,分别为16.0％,28.5％,41.8％,对照组的阳性表达率不足5％。Hp阳性组PKC表达阳性率(47/130,36.2％)高于Hp阴性组(6/41,14.6％.P=(0.010)。PKC表达组,其P53表达的阳性率和阳性表达程度均高于PKC无表达的病例,在肠化生组统计学检验差异有显著性(75.0％ vs 28.6％,P=0.012),不典型增生(66.7％ vs 50.0％,P=0.430)和胃癌(63.6％ vs 52.2％,P=0.310)统计学检验差异无显著性。结论在从慢性胃炎到肠上皮化生、不典型增生、胃癌的发生过程中,存在PKC表达水平的增高、PAIM To explore the mechanism of Hp infection on the development of gastric cancer by simultaneously detecting Hp infection, PKC level, cell proliferation level and expression of p53 mutation of different gastric mucosae, from chronic gastritis, intestinal metaplasia, dysplssia and gastric cancer. METHODS A case-control study was conducted. A total of 185 cases including 52 with intestinal metaplasia (IM), 44 with dysplasia (Dys), 89 with gastric cancer (GC) and 38 control with chronic gastritis (CG) were collected in Zhongshan Hospital from Jan. 1994 to Dec. 1995. All subjects were examined by gastroendoscopy, and Hp status determined by Rapid Urease Test and pathologic Giemsa staining.Immunohistochemical assay was performed to study the expression of PKC (EnVision^(TM)), proliferating cell nuclear antigen (PCNA) and P53 protein. RESULTS The overall Hp infection rate was 76.2%(138/181). The rates of Hp infection were higher in IM (62.0%, 31/50), Dys (88.6%, 39/44) or GC (78.3%, 68/87) than that In CG (52.6%, 20/38, P<0.05). There was no significant difference of PCNA labeling index among the groups (IM, 42.0%±26.0%, Dys, 36.5%±28.8%, GC, 41.1%±25.5%, CG, 35.4%±29.7%). The index was higher in group with Hp positive than that in group with Hp negative. The expression of mutant p53 gene was higher in Dya or GC than that in IM. It was also higher in patients with Hp positive than that with Hp negative in IM group (48.5% vs 15.8%, P=0.020), but no significant difference In Dys group (53.9% vs 60.0%, P=0.794) and GC group (53.8% vs 68.4%, P=0.258). There was a higher PCNA labeling index in patients with P53 expression than those without P53 expression. PKC expression rates were higher in IM (16.0%), Dys (28.5%) or gastric cancer (41.8%) than that in the control group (5%). PKC expression rates were higher in patients with Hp positive (36.2%) than that with Hp negative (14.6%, P=0.010). The expression rate of P53 was higher in patients with PKC positive than that in PKC negative, especially in IM group. CONCLUSION T

关 键 词：幽门螺杆菌 蛋白激酶C 癌前状态 癌基因 肠化生 突变 基因表达 免疫组织化学 

分 类 号：R735.2[医药卫生—肿瘤]