胃癌幽门螺杆菌感染中c-met基因表达与增殖的关系及其预后

目的 研究c-met基因蛋白及增殖细胞核抗原（PCNA）在幽门螺杆菌（Hp)感染的胃黏膜病变演进中的表达及关系，探讨Hp感染对胃癌预后的意义。方法 采用免疫组织化学法检测145例经病理证实不同胃黏膜病变的c-met和PCNA基因表达，Warthin-Starry法检测Hp感染。结果 在浅表性胃炎（CSG）、萎缩肠化性胃炎、异型增生（DYS）、早期胃癌和进展期胃癌中，c-met和PCNA2种基因在萎缩肠化性胃炎、DYS、胃癌均显著高于CSG（P＜0．05）。对胃黏膜增殖程度与c-met和PCNA阳性表达强度的密切关系分析，表明两者有显著关联（P＜0．01）。c-met和PCNA阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关，而且Borrmann Ⅳ明显高于早期胃癌（P＜0．05）。c-met－LI和PCNA－LI在胃癌中等级相关表达有极显著的相关性（P＜0．001）。c-met阳性表达与肠型胃癌Hp感染有关。萎缩肠化性胃炎、DYS和胃癌组c-met阳性表达中Hp感染者明显高于阴性者。Hp阳性者5年生存期显著短于Hp阴性者。结论 c-met和PCNA基因表达与胃黏膜增殖和恶化有关，c-met基因可能成为评估胃癌恶化和预后的1项新的重要指标。Hp感染和c-met表达与胃黏膜增殖和恶化有关，Hp感染与胃癌预后有关。     

胃癌中幽门螺杆菌感染与原癌基因c—met表达及预后研究

目的　研究幽门螺杆菌(Hp)感染的胃癌(GC)组织中c-met表达及(Hp)感染对胃癌预后的影响。方法　经病理证实,不同病变胃粘膜145例以免疫组化检测c-met基因表达,以W-S法及快速尿素酶试验检测(Hp)感染。结果　在浅表性胃炎(CSG)、萎缩肠化生胃炎(CAG+IM)、异型增生(DYS)、早期GC和进展期GC中,c-met基因表达率分别为25.53%,51.28%,61.54%,66.67%和68.42%,CAG+IM、DYS、GC均显著高于CSG(P＜0.05)。肠型胃癌c-met阳性表达与(Hp)感染密切相关。CAG+IM,DYS和GC组c-met阳性表达(Hp)感染者明显高于阴性组。(Hp)阳性者5年生存期显著短于(Hp)阴性者。结论　(Hp)感染和c-met表达与胃粘膜增殖和恶化有关,前者也与胃癌预后有关。     

Prevalence of subtypes of intestinal metaplasia in gastric antral mucosa

A prospective gastroscopic-bioptic study of 533 patients was performed to assess the prevalence and distribution of intestinal metaplasia (IM) and its subtypes in the antral mucosa of patients with various upper intestinal disorders and to assess whether the presence of certain IM subtypes might be of help in selecting patients for careful endoscopic-bioptic surveillance in the screening for gastric carcinoma. IM was found in 135 patients (25.3%). Its prevalence increased with age (P<0.001) and was strongly associated with intestinal-type carcinoma as compared to diffuse-type carcinoma (P<0.001), gastritis (P<0.001), and gastric ulcer (P<0.05). Type I IM was predominant (98.5%), whereas types II and III IM, respectively, were found in 77.8% and 15.6% of the patients with IM. No difference in the prevalence of type I and II IM was found among the various gastric disease states. Type III IM was strongly associated with intestinal-type carcinoma as compared to either benign lesions (P<0.01) or diffuse-type carcinoma. These results suggest that type III IM may play a special role in the histogenesis of intestinal-type carcinoma and suggest that the finding of this IM subtype in gastric biopsies may possibly be of help in identifying patients at greater risk of developing carcinoma.     

幽门螺杆菌感染在胃癌及癌前病变中的研究

目的　研究胃癌及癌前病变与Hp感染的关系 ,以探讨Hp可能的致癌机制。 方法　经内镜和病理明确诊断的胃癌及癌前病变者共 5 48例 ,包括慢性浅表性胃炎 (CSG) 16 3例、慢性萎缩性胃炎 (CAG) 2 0 7例、肠上皮化生 (IM) 71例 ,异型增生(DYS) 4 5例及胃癌 (GC) 6 2例。每例均活检胃窦大小弯、胃角及胃体大小弯共 5块 ,以WS法检测Hp。结果　癌前病变及胃癌Hp感染均较高 ,CAG(4 2 .5 % ) ,IM(76 .1% ) ,DYS(88.9% )和GC(72 .5 % ) ,与CSG(2 3.9% )有显著性差异 (P <0 .0 5或P <0 .0 1)。随着年龄增大 ,CAG、IM、DYS和GC逐步增多 ,而且≥ 5 6岁年龄组IM、DYS和GC显著多于≤ 40岁组 (P <0 .0 5 ) ,但CSG则相反。肠型胃癌和Hp感染密切相关 (P <0 .0 5 ) ,从胃窦小弯和大弯、胃角及胃体小弯和大弯顺序 ,Hp感染随着CSG、CAG、IM、DYS和GC病变而增高 ,Hp感染部位也在上移 ,尤其在胃体小弯及大弯 ,IM、DYS和GC的Hp感染显著高于CSC部位 (P <0 0 5 )。结论　Hp感染是导致从胃炎→胃萎缩→肠化→异型增生→癌变序列发展的危险因子 ,肠型胃癌和Hp感染密切相关 ,胃镜检查应该多部位取活检作病理及Hp检测 ,尤其是高位     

Expression of nuclear factor-kappa B and target genes in gastric precancerous lesions and adenocarcinoma： Association with Helicobactor pylori cagA （＋） infection

AIM:To examine the expression of nuclear factor kappaB (NF-κB) and its target genes in intestinal metaplasia (IM),dysplasia (DYS) and gastric carcinoma (GC) infected with Helicobacter pylori (H pylori) and to investigate the mechanism underlying Hpyloricytotoxin associated gene A(cag A) infection leading to gastric adenocarcinoma.METHODS: Expressions of NF-κB/p65 and its target genes:c-myc, cyclinD1 and bcl-xl were immunohistochemically examined in 289 cases of gastric biopsy and resection specimens from patients with IM, DYS and GC infected with H pylori. H pylori in the above mentioned tissues was detected by Warthin-Starry stain and rapid urease tests.IgG antibody to cagA in sera of the patients was measured by ELISA.RESULTS:The positive rates of NF-κB/p65 were significantly higher in groups with cagA of IMI-Ⅱ(28/33), IM III(48/52),DYSI(27/31), DY5 Ⅱ-Ⅲ(28/32), GC(35/40) than in groups without cagA of IMI-Ⅱ(4/17), IMⅢ(3/20), DYSI(3/20),DYSⅡ-Ⅲ(6/21), GC(10/23). The expressions of c-myc,cyclinD1, and bcl-xl were significantly higher in groups with cagA of IM Ⅲ(47/52, 49/52, 46/52), DYSⅡ-Ⅲ(29/32, 26/32,25/32) than in groups without cagA of IM Ⅲ(8/20, 7/20,5/20), DYSⅡ-Ⅲ(10/21, 8/21, 3/21), which were in conformity with the expression of NF-κB in IM Ⅲ, and DYSⅡ-Ⅲ. Asignificantly higher expression level of NF-κB/p65, c-myc,cyclinD1 and bcl-xl was detected in intestinal type GC(27/28,18/28, 22/28, 24/28) than in diffuse type GC(8/12, 3/12,3/12, 6/12), respectively.CONCLUSION: There may be two different molecular mechanisms in the occurrence of intestinal and diffuse type gastric carcinomas. Intestinal type gastric carcinoma is strongly associated with high expression of c-myc, cyclinD1 and bcl-xl through NF-κB/p65 activated by Hpylori cagA.Inhibiting the activity of NF-κB is an effective and promising way to prevent intestinal type gastric carcinoma.     

Expression of Span-21 and Ypan-21 in gastric cancer and subtypes of intestinal metaplasia

AIM: To analyze the relationship between intestinal metaplasia (IM) and gastric cancer (GC). METHODS: The expression of the Span-1 and Ypan-1 antigens in GC (n = 110) and IM (n = 343) specimens was examined using the ABC immunohistochemical technique. RESULTS: The expression rates of Span-1 and Ypan-1 in well and moderately differentiated adenocarcinoma (85.4% and 70.0%, respectively), signet-ring cell carcinoma (80.0%, 88.7%) and mucinous adenocarcinoma (88.6%, 76.5%) were significantly higher than the rates in poorly differentiated adenocarcinoma (48.6%, 45.9%), whereas the difference between early GC (59.2%, 65.4%) and advanced GC (73.8%, 65.5%) was insignificant. For IM, the expression of Span-1 was significantly higher in dysplasia, IM with GC, and chronic atrophic gastritis than in chronic superficial gastritis. In contrast, the expression of Ypan-1 was significantly higher only in IM with dysplasia (65.5%) than in chronic superficial gastritis (39.3%). When IM was classified into types I, II and III, the expression of both antigens in type III (79.0%, 75.2%) was higher than in type I (42.3%, 45.5%) and type II (51.2%, 50.0%), which themselves were similar. CONCLUSION: Span-1 and Ypan-1 may be of value in detecting GC, even in the early stage, and type III IM should be considered precancerous.     

胃癌及癌前病变胃粘膜的粘液组织化学研究

本文应用粘液组织化学方法对168例肠化生、96例异型增生和89例胃癌胃粘膜活检标本进行观察,发现87.6％的胃癌和40.6％的异型增生组织有异常粘液分泌;不全结肠型肠化生和硫酸粘液阳性肠化生在癌旁和异型增生的检出率显著地高于萎缩性胃炎组(P<0.05);伴不全结肠型肠化生和伴其它型肠化生的胃癌患者平均年龄分别为59.5岁和54.4岁、男女比为6∶1和2.25∶1.结果提示有异常粘液分泌的异型增生、伴不全结肠型化生的异型增生、不全结肠型化生的高龄男性、伴不全结肠型化生的胃良性疾病和硫酸粘液阳性肠化生宜被看作是胃癌的癌前病变,其中前三组的癌变趋向性更大.     

胃幽门螺杆菌感染与抑癌基因失活的关系

目的探讨胃癌及癌前病变组织中幽门螺杆菌(H.pylori)感染与抑癌基因失活间的相互关系.方法运用DNA-PCR技术检测H.Pylori感染,采用PCR-RFLP,PCR-SSCP,RT-PCR及免疫组化技术分析182例胃癌及癌前病变及正常胃粘膜中抑癌基因APC,MCC,DCC,YNZ22及p53基因的杂合缺失、突变、mRNA及蛋白异常表达.结果胃癌及癌前病变组织中H.pylori的感染率(IM61.7%,Dys 63.3%,GC 42.3%)显著高于正常胃粘膜(17.5%,P＜0.05).但胃癌及癌前病变间H.pylori感染率无显著差别(P＞0.05),胃肠两型胃癌中H.pylori感染率分别为47.1%及42.2%,两者无显著差别(P＞0.05).胃癌及癌前病变组织中存在多种抑癌基因失活.H.pylori感染与癌前病变-肠化生中APC基因异常蛋白表达有关(Hp+43.2%vsHp-13.0%,P＜0.05).胃癌组织H.pylori感染阳性组中APC基因突变(50.0%)及蛋白表达(63.6%)、p53基因蛋白表达率(59.1%)显著高于阴性组(vs16.7%,P＜0.05;vs30.0%,P＜0.01;vs20.0%,P＜0.01).结论幽门螺杆菌感染及多种抑癌基因失活可能与胃癌的发生发展相关,H.pylori感染与APC,p53基因失活可能相关.     

Expression of 1A6 gene and its correlation with intestinal gastric carcinoma

AIM: To investigate the expression of 1A6 gene in the lesionsduring the development of intestinal gastric carcinoma.METHODS: One hundred and thirty-six cases of intestinalmetaplasia (IM) from surgical resections and biopsy wereclassified by mucous staining. Expression of 1A6 in all caseswas detected using immunohistochemical S-P method.RESULTS: The positive rates of 1A6in normal and superficialgastritis (SG), severe atrophic gastritis (SAG), type Ⅰ, Ⅱ, ⅢIM, dysplasia (Dys) and intestinal gastric carcinoma (IGC)were 12.2 %, 16.7 %, 7.1%, 22.6 %, 47.8 %, 46.9 % and60.8 %, respectively. A significant difference among typeⅢ IM and SG, SAG, type I and Ⅱ IM was found (P＜0.01),the difference between type Ⅲ and Dys, IGC being notsignificant.CONCLUSION: As a new tumor-related gene, expression of1A6 may be an effective parameter to predict the malignanttransformation of precancerous lesion to gastric carcinoma.     

老年人胃癌癌前变化的随访研究

目的 研究老年人胃癌癌前变化的胃癌发病率,确定老年人发生胃癌的危险因素. 方法 完成随访的287例对象入选时平均年龄(79.44±11.69)岁,其中男204例,女83例.在1980年1月至2009年6月期间胃镜病理诊断为胃癌癌前变化,每隔1～3年随访胃镜及活检.对发生胃癌的危险因素进行logistic回归分析,计算OR值及其95％可信区间. 结果 入选对象胃镜病理诊断萎缩性胃炎177例,肠化生75例(其中Ⅰ型36例,Ⅱ型20例,Ⅲ型19例),低级别上皮内瘤变35例.随访共发现胃癌21例,胃癌发生率为7.32％,年平均发生率0.75％.其中继发于萎缩性胃炎4例,胃癌发生率为2.26％,年平均发生率0.23％；Ⅰ型肠化生1例,胃癌发生率为2.78％,年平均发生率0.29％；Ⅱ型肠化生1例,胃癌发生率为5.00％,年平均发生率0.51％;Ⅲ型肠化生6例,胃癌发生率为31.58％,年平均发生率3.25％；低级别上皮内瘤变9例,胃癌发生率为25.71％,年平均发生率2.65％.有吸烟史、低级别上皮内瘤变和Ⅲ型肠化生分别是胃癌发生的危险因素. 结论 老年人胃癌癌前变化的胃癌年平均发生率为0.75％,吸烟、低级别上皮内瘤变和Ⅲ型肠化生是老年人发生胃癌的危险因素.应加强对老年人胃癌癌前变化的胃镜监测.     

Different types of intestinal metaplasia and gastric cancer: a clinico-endoscopic follow-up of 112 cases

The expression of 9 tumor-associated antigens (MG7-, MGd1-, MC3-corresponding antigens and CEA, P21ras, sialoglycoprotein, CA19-9-like, sialo-Tn and Lea-like antigens) were investigated on biopsy specimens with different types of intestinal metaplasia (types I, II and III) taken from 112 patients with benign gastric conditions. The incidences of positive staining for all antigens but P21ras in type III intestinal metaplasia were significantly higher than those in types I and II (P less than 0.05-0.001). These 112 patients with intestinal metaplasia were clinico-endoscopic followed-up for 15-70 months. Five of them were found to develop gastric carcinoma within 25-60 months with a cancer detection rate of 4.5%. All the five malignancies were detected in patients with type III (16.1%), none was found in those with types I and II, these differences were significant (P less than 0.05-0.01). Our results indicate that type III intestinal metaplasia has a higher potentiality to evolve to malignancy and that MG7, MGd1, MC3, CEA, CA19-9-like and sialo-Tn antigens are valuable tumor markers in defining the high-risk group of gastric cancer.     

原位逆转录PCR检测胃癌及癌前组织中端粒酶RNA及其临床意义

目的　研究胃癌及癌前病变胃粘膜端粒酶RNA的检测及其临床意义。方法　选取经病理组织学证实的胃粘膜活检标本 15 0例 ,包括慢性浅表性胃炎 3 2例、肠上皮化生 3 6例、不典型增生 3 4例、胃癌 48例 ,采用原位逆转录PCR、端粒重复序列扩增 (TRAP)法检测上述胃粘膜端粒酶RNA与端粒酶活性。结果　原位逆转录PCR技术检测胃粘膜活检标本端粒酶RNA阳性率为 5 5 .3 % (83 / 15 0 ) ,显著高于TRAP法检测端粒酶活性阳性率 (4 0 .0 % ,60 / 15 0 ) ,P <0 .0 5。端粒酶RNA在胃癌及癌前病变 (包括肠上皮化生与异型增生 )中检出率显著高于浅表性胃炎 (P <0 .0 5 ) ,胃癌中端粒酶RNA检出率亦显著高于肠上皮化生及不典型增生 (P <0 .0 5 ) ,但后两者比较差异无显著性 (P >0 .0 5 )。端粒酶RNA主要分布于胃粘膜癌细胞及癌前病变上皮细胞的胞核内。结论　端粒酶RNA与胃癌的发生密切相关。原位逆转录PCR技术检测胃粘膜端粒酶RNA对胃粘膜癌变的早期诊断和预测有重要价值 ,而且可能是较端粒酶活性更灵敏的生物学指标     

胃癌中幽门螺杆菌感染与胃粘膜增殖及凋亡研究

目的研究幽门螺杆菌(Hp)感染的胃癌(GC)发展中增殖细胞核抗原(PCNA)表达及细胞凋亡的关系和对胃癌预后意义。方法145例经病理证实,不同胃黏膜病变采用免疫组化检测PCNA基因表达及Warthinstarry法检测Hp感染。采用原位末端标记法(TUNEL)检测细胞凋亡。结果在浅表性胃炎(CSG)、萎缩肠化生胃炎(CAG+IM)、异型增生(DYS)、早期GC和进展期GC中,PCNA基因表达率分别为24.53%,46.28%,60.54%,57.67%和71.42%,CAG+IM、DYS、GC均显著高于CSG(P<0.05)。凋亡指数(AI)分别为(4.55±2.33)%、(6.43±5.60)%、(6.45±5.12)%、(6.55±4.80)%、(8.84±5.63)%,进展期GC显著高于CSG(P<0.05)。胃黏膜凋亡指数与PCNA表达强度有密切相关(P<0.05)。PCNA阳性表达与胃癌组织类型、浆膜浸润和淋巴结转移密切相关,而且BorrmannIV明显高于早期胃癌和BorrmannI,II(P<0.05)。PCNA阳性表达与肠型胃癌Hp感染有关。CAG+IM,DYS和GC组PCNA阳性表达中Hp感染者明显高于阴性者。Hp阳性者5年生存期显著短于Hp阴性者。结论Hp感染和PCNA表达与胃黏膜增殖和恶化有关,且与凋亡有相关性。Hp感染与胃癌预后有关。     

Histochemical studies on intestinal metaplasia adjacent to gastric cardia adenocarcinoma in subjects at high-incidence area in Henan, north China

AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Linzhou, Henan Province, China. METHODS: Alcian-blue-periodic acid Schiff and high iron diamine-Alcian blue histochemical methods were performed on 142 cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were from Linzhou, Henan Province, China, the highest incidence area for both GCA and squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients before surgery. RESULTS: The detection rate of IM in tissues adjacent to GCA tissues was 44.9%, which was significantly lower than that in GC tissues (80.64%, P<0.01). The rates of both incomplete small intestinal and colonic IM types identified by histochemistry in GCA tissues (31.82% and 63.64%, respectively) were significantly higher than those in GC (5.33% and 21.33%, respectively, P<0.01). CONCLUSION: IM in GCA and GC should be considered as a separate entity. Further research is needed to evaluate whether neoplastic progression of IM is related to its mucin profile in GCA.     

Histochemical studies on intestinal metaplasia adjacent to gastric cardia adenocarcinoma in subjects at high-incidence area in Henan, north China

AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Linzhou, Henan Province, China.METHODS: Alcian-blue-periodic acid Schiff and high iron diamine-Alcian blue histochemical methods were performed on 142 cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were from Linzhou, Henan Province, China, the highest incidence area for both GCA and squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients before surgery.RESULTS: The detection rate of IM in tissues adjacent to GCA tissues was 44.9%, which was significantly lower than that in GC tissues (80.64%, P<0.01). The rates of both incomplete small intestinal and colonic IM types identified by histochemistry in GCA tissues (31.82% and 63.64%, respectively) were significantly higher than those in GC (5.33% and 21.33%, respectively, P<0.01).CONCLUSION: IM in GCA and GC should be considered as a separate entity. Further research is needed to evaluate whether neoplastic progression of IM is related to its mucin profile in GCA.     

胃癌与癌前病变关系的研究

目的观察胃癌（ＧＣ）的发生过程．方法在胃癌高发区山东省临朐县，对一组有胃粘膜病理诊断结果的自然人群进行随访观察，并配以嵌套式病例对照研究．结果胃粘膜肠上皮化生（ＩＭ）和异型增生（Ｄｙｓ）发生胃癌的危险性显著高于慢性萎缩性胃炎（ＣＡＧ），且在胃中不同部位的检出率与胃癌在相应部位发生的频率存在正等级相关关系；Ｄｙｓ发生胃癌所需要的时间明显短于ＩＭ发生胃癌所需要的时间．结论胃癌特别是肠型胃癌是在ＣＡＧ基础上发生ＩＭ，进而产生Ｄｙｓ，最终导致癌变的一系列过程     

Expression of ornithine decarboxylase in precancerous and cancerous gastric lesions

AIM: To investigate the expression of ornithine decarboxylase (ODC) in precancerous and cancerous gastric lesions. METHODS: We studied the expression of ODC in gastric mucosa from patients with chronic superficial gastritis (CSG,n = 32),chronic atrophic gastritis CAG,n = 43; 15 with and 28 without intestinal metaplasia (IM),gastric dysplasia (DYS,n = 11) and gastric cancer (GC,n = 48) tissues using immunohistochemical staining. All 134 biopsy specimens of gastric mucosa were collected by gastroscopy. METHODS: The positive rate of ODC expression was 34.4%,42.9%,73.3%,81.8% and 91.7% in cases with CSG,CAG without IM,CAG with IM,DYS and GC,respectively (P < 0.01),The positive rate of ODC expression increased in the order of CSG < CAG (without IM) < CAG (with IM) < DYS and finally,GC. In addition,ODC positive immunostaining rate was lower in well-differentiated GC than in poorly-differentiated GC (P < 0.05). CONCLUSION: The expression of ODC is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. This finding indicates that ODC may be used as a good biomarker in the screening and diagnosis of precancerous lesions.     

微卫星不稳定性与胃癌发生关系的研究

目的 探讨微卫星不稳定性(MSI)在胃癌及癌前病变组织中的发生规律及其在胃癌发生过程中的作用。方法 对30例胃癌、30例异型增生、40例肠上皮化生组织标本分别提取病变及相应正常组织的DNA，应用银染PCR—SSCP技术检测5个微卫星位点的不稳定性。结果 肖癌组织MSI的发生率为23．3％，胃窦癌MSI的发生率显著高于贲门癌(P=0．044)。异型增生组织的MSI发生率为30％，肠上皮化生组织MSI发生率为20％，且全部出现在中度以上肠化生组织中。结论 MSI是胃癌多步骤发生过程中的早期分子事件，可能有助于胃黏膜细胞恶性转化表型的获得，在胃癌的形成过程中具有重要作用。