Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia

Loss of Sonic Hedgehog (Shh) and aberrant CDX2 expression are early changes correlating with the presence of intestinal metaplasia that occur in the gastric mucosa prior to neoplastic transformation. The aim of this study was to compare the improvement in corpus gastritis with Shh and CDX2 expression after H. pylori eradication between subjects at high risk for gastric cancer and controls. The usefulness of serum pepsinogen levels as a predictor of resolved corpus gastritis was also examined. Seventy patients with endoscopic resection for early gastric cancer and 30 controls were studied. Expression of Shh and CDX2 were evaluated by immunostaining. Serum levels of pepsinogen I before eradication in the patients scored as having improvement of corpus atrophy were significantly higher than in the patients without improvement (<0.01). Residual inflammation at the corpus lesser curve was more frequently detected in the cancer group than in the controls (OR 4.6 95% C.I. 1.6-13.5) and in the mucosa with incomplete intestinal metaplasia rather than in those without incomplete intestinal metaplasia (OR 7.6 95% C.I. 2.4-24.3). Atrophy, expression of Shh and CDX2 at the corpus lesser curve significantly improved in mucosa without incomplete intestinal metaplasia (p < 0.01), but not in mucosa with incomplete intestinal metaplasia. In conclusion, H. pylori eradication prior to development of incomplete intestinal metaplasia improves corpus gastritis and may prevent gastric cancer. Pepsinogen I may be a useful marker in patients with a residual higher risk of gastric cancer after H. pylori eradication.     

PCNA在胃粘膜肠上皮化生、异型增生和胃癌中表达及意义的研究

目的研究增殖细胞核抗原(PCNA)在胃粘膜、肠上皮化生,异型增生及胃癌中的表达.评估胃癌前病变的发展趋势,进一步探讨胃癌发生的分子生物学机制.方法应用免疫组化技术测定115例患者的PCNA表达情况.其中50例肠上皮化生、15例异型增生、50例胃癌.结果PCNA的表达从肠上皮化生、异型增生到胃癌呈递增趋势.在肠上皮化生为轻度表达,异型增生以中度表达为主,而胃癌多呈重度和过度表达.PCNA强阳性表达与胃癌分化程度,侵润深度,淋巴结转移密切相关.结论PCNA在胃粘膜不同疾病细胞核内的表达、反映了细胞增殖状态和生长速度、有助于判断肠上皮化生、异型增生的发展趋势及判断与监测胃癌的预后.     

MUC-5AC核粘蛋白在早期胃癌中的表达和意义

目的探讨胃正常粘膜、不典型增生以及早期胃癌中MUC-5AC核粘蛋白的表达状态及临床病理意义.方法应用免疫组织化学s-p法检测人正常胃粘膜、不典型增生及早期胃癌组织中的表达.结果人正常胃粘膜中浅表1/3范围内广泛分布MUC-5AC核粘蛋白(100%).不典型增生和早期胃癌组织中表达的阳性率分别为70%和41.7%.早期胃癌中MUC-5AC核粘蛋白的表达与患者的性别、肿物的部位、大小、浸润深度、淋巴结转移和分化程度、异型度及癌旁肠化生和癌旁淋巴反应无关(P＞0.05).但与Laurem's分型(肠型、胃型、混合型)密切相关,且差异显著(P＜0.05).结论 MUC-5AC核粘蛋白在胃粘膜不典型增生和胃癌早期阶段即出现不同程度的异常表达,整个过程呈下调趋势.且与Lauren's分型密切相关.     

慢性胃病伴肠上皮化生、胃癌与幽门螺旋杆菌感染的关系

目的探讨慢性胃病伴肠上皮化生、胃癌与幽门螺旋杆菌（helicobacter pylore,HP）感染的关系。方法采用warthin—strarry银染色方法,对380例慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织进行HP检测．应用（alcianblue—PH2．5-periodic—schiff,AB—PAS）、（high-iron—diamine-alcianblue—PH2．5,HID-AB）黏液组织化学方法,区别慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织伴有肠上皮化生的类型。结果总例数380例。HP阳性率为69．74％。慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织伴肠上皮化生的HP感染率分别为77．78％、85．71％、100．00％、80．95％。慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡及胃癌的癌旁组织伴肠上皮化生AB—PAS染色阳性率分别为86．84％、91．43％、93．33％、100．00％;HID—AB染色阳性率分别为34．21％、42．86％、53．33％、85．71％。癌旁组织的肠上皮化生中,78．57％为不完全大肠型,慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡伴肠上皮化生中,不完全小肠型比例分别为52．63％、54．28％、53．33％;不完全大肠型比例分别为28．95％、31．43％、20．00％。结论HP感染与慢性胃病伴肠上皮化生及胃癌的发生密切相关。癌旁组织的不完全大肠型肠上皮化生与胃癌的发生密切相关;慢性胃病组织当中的小灶状不完全大肠型上皮化生具有潜在发生癌变的可能性。     

老年患者的幽门螺杆菌（HP）感染与胃癌及癌前病变中C-myc、p16、p53、K-ras和C-erbB-2基因表达

目的探讨老年患者幽门螺杆菌（HP）感染与胃癌及癌前病变中C-myc、p16、p53、K-ras和C．erbB-2基因表达及其临床意义。方法分析老年患者的胃镜检查活检标本116例,HE染色观察胃黏膜的炎症和异型增生变化,特染法检测胃黏膜的肠上皮化生,应用Warthin-stary银染色法检测HP,应用ELISA法检测血清学HPIgG,14C尿素呼气试验（14C-UBT）检测HP,应用免疫组化sP法检测C-myc、p16、p53、K-ras和C-erbB-2基因的表达。结果老年患者在不同胃组织中C-myc、p16、p53基因的表达均有显著差异,而K-ras和C-erbB-2基因表达未见显著性差异。HP感染率以胃癌为最高,其次为胃溃疡。结论本实验通过老年患者的HP检测和观察胃黏膜的炎症和异型增生变化,再结合癌基因和抑癌基因的表达异常,提示萎缩性胃炎异型增生、肠上皮化生和胃癌的HP感染率均高于非萎缩性胃炎。再次表明胃癌与HP感染有一定相关性。     

Site-dependent Development of Complete and Incomplete Intestinal Metaplasia Types in the Human Stomach

The topographical distribution of complete and incomplete types of intestinal metaplasia in human stomach samples was investigated in order to elucidate their mutual histogenetic relationship and significance in carcinogenesis. Subgross stereomicroscopic examination of alcian blue and hematoxylin-stained gastric mucosae allowed clear distinction of complete and incomplete intestinal metaplasia types as white (with or without purple hue) and purple foci, respectively, against the background magenta areas of non-intestinalized mucosa. Intestinal metaplasias which developed in the fundic area were predominantly of the complete type whereas those of the antrum were a mixture of both with a distinct predilection for expression of the incomplete type. Although there was some variation among foci regarding the hue of white or purple, the color feature was principally homogeneous within each individual intestinal metaplasia focus. Thus phenotypic analysis indicated intestinal metaplasia expression to be clearly influenced by intragastric topography. The study did not provide any evidence that a shift from incomplete to complete type intestinal metaplasia may occur with time or that the incomplete type may be more intimately associated with development of well-differentiated carcinomas.     

Site-dependent development of complete and incomplete intestinal metaplasia types in the human stomach.

The topographical distribution of complete and incomplete types of intestinal metaplasia in human stomach samples was investigated in order to elucidate their mutual histogenetic relationship and significance in carcinogenesis. Subgross stereomicroscopic examination of alcian blue and hematoxylin-stained gastric mucosae allowed clear distinction of complete and incomplete intestinal metaplasia types as white (with or without purple hue) and purple foci, respectively, against the background magenta areas of non-intestinalized mucosa. Intestinal metaplasias which developed in the fundic area were predominantly of the complete type whereas those of the antrum were a mixture of both with a distinct predilection for expression of the incomplete type. Although there was some variation among foci regarding the hue of white or purple, the color feature was principally homogeneous within each individual intestinal metaplasia focus. Thus phenotypic analysis indicated intestinal metaplasia expression to be clearly influenced by intragastric topography. The study did not provide any evidence that a shift from incomplete to complete type intestinal metaplasia may occur with time or that the incomplete type may be more intimately associated with development of well-differentiated carcinomas.     

胃粘膜肠化与胃癌关系的粘液组织化学研究

本文应用粘液组织化学技术，对117例胄癌、62例慢性胃炎伴（肠化生）组织的粘液分泌进行观察。根据所含粘液不同，将胄癌分为肠型及胃型，将畅化分为大肠型及小肠型。肠型胃癌的肠化检出率显著高于胃型胃癌（P＜0．01）。大肠型肠化在肠型胃癌旁肠化检出率显著高于在胄型胄癌旁肠化及慢性胃炎伴肠化的检出率（P＜0．01）。肠型胃癌的发生与胄粘膜肠化，特别与大肠型肠化关系密切。因此，加强对大肠型肠化的密切随访．有利于胃癌的早期发现。     

用BC2单抗检测胃癌及癌前病变组织中MUC1基因表达及其意义

 目的　揭示胃癌及肠化组织中MUC1基因的表达与其临床病理行为之间的联系。方法　用BC2抗体和免疫组化SP法检测人正常胃肠道粘膜、肠化粘膜以及胃癌组织中MUC1基因核心肽的表达。结果　人正常胃粘膜组织中广泛分布MUC1基因产物(100%),抗原主要位于上皮层和胃腺的中下部;肠化和胃癌组织中的表达阳性率分别为79.3%和82.6%;胃癌组织中MUC1基因表达与患者的性别、部位、大小、淋巴结转移、分化类型、浸润深度、临床分期和Lauren氏分型之间无关(P>0.05);但MUC1基因强阳性者与中弱阳性者之间的临床分期存在明显的差别(P<0.05),表达越强,Ⅰ～Ⅱ期的可能性越小;不同类型肠化中MUC1基因的表达无差异(P>0.05)。结论　上述结果提示用BC2抗体检测的MUC1基因可能是胃癌进展的有用标志,可能与胃癌患者的临床病理行为之间有关,而与肠化分型无关。     

幽门螺旋杆菌感染胃黏膜COX-2和P-gp表达与胃癌发生

背景与目的通过检测幽门螺旋杆菌(Helicobacter Pylori,H.pylori)感染胃粘膜组织环氧合酶-2(Cyclooxygenase-2,COX-2)和多药耐药-1(Multidrug resistance-1,MDR-1)基因表达产物P糖蛋白(P-glycoprotein,P-gp)表达,探讨幽门螺旋杆菌相关胃癌的发生机制,以及P-gp高表达的机制。材料与方法慢性胃炎155例(30例慢性浅表性、40例慢性萎缩性、45例肠化、40例非典型增生)及胃癌80例(肠型40例,弥漫型40例),COX-2和P-gp表达检测选择免疫组化S-P法,H.pylori感染检测采用快速脲素酶及改良Giemsa染色方法。结果H.pylori阳性感染率、COX-2和P-gp的阳性表达率,肠型胃癌均明显高于弥漫型胃癌(P<0.01)。慢性萎缩性胃炎、肠化、非典型增生及肠型胃癌中H.pylori感染与COX-2的表达呈正相关(P<0.01)。H.pylori感染的慢性浅表性胃炎、慢性萎缩性胃炎、肠化、非典型增生及肠型胃癌中COX-2的表达与P-gp的表达也均呈正相关(P<0.01)。结论H.pylori依赖的COX-2表达与P-gp表达有关,可能有助于胃癌形成以及胃癌对化疗抵制。     

Monocyte chemoattractant protein‐1 is generated via TGF‐β by myofibroblasts in gastric intestinal metaplasia and carcinoma without H. pylori infection

Helicobacter pylori (H. pylori) stimulates secretion of monocyte chemoattractant protein 1 (MCP‐1) from gastric mucosa. Monocyte chemoattractant protein‐1 (MCP‐1) expression and macrophage infiltration are recognized in human gastric carcinoma. We have previously generated Cdx2‐transgenic mice as model mice for intestinal metaplasia. Both chronic H. pylori‐associated gastritis and Cdx2‐transgenic mouse stomach develop intestinal metaplasia and finally gastric carcinoma. In this study we have directed our attention to MCP‐1 expression in the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2‐transgenic mouse stomach. Quantitative real‐time PCR was performed to determine MCP‐1 and transforming growth factor‐β1 (TGF‐β1) mRNA expression levels and single‐ or double‐label immunohistochemistry was used to evaluate the localization of MCP‐1, TGF‐β type I receptor, and α‐smooth muscle actin (αSMA). We determined that MCP‐1 mRNA dramatically increased in the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2‐transgenic mouse stomach, compared with normal mouse stomach. Both MCP‐1 and TGF‐β type I receptor were co‐expressed in the αSMA‐positive myofibroblasts of intestinal metaplastic mucosa and gastric carcinoma. Exogenous application of TGF‐β1 increased MCP‐1 mRNA expression levels in the intestinal metaplastic tissue. Furthermore, TGF‐β1 was overexpressed and macrophage was strongly infiltrated in the gastric carcinoma. In conclusion, MCP‐1 expression, which was stimulated by TGF‐β1, was recognized in the TGF‐β type I receptor‐expressing myofibroblasts of the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2‐transgenic mouse stomach. The present results suggest that intestinal metaplasia and gastric carcinoma themselves induce MCP‐1 expression independently of H. pylori infection. (Cancer Sci 2010)     

Villin蛋白的表达及其与贲门腺癌的关系

目的 探讨Villin蛋白在贲门肠化中的作用及其与贲门腺癌(GCA)发生、发展的关系.方法 采用免疫组织化学S-P法检测128例胃镜活检及手术切除的GCA及癌旁肠化组织中Villin蛋白的表达,其中贲门肠化组织25例、肠化伴不典型增生组织48例,GCA组织55例,并选取15例胃镜普查正常贲门组织作为对照.结果 Villin蛋白在正常贲门组织中无阳性表达,在贲门肠化组织中的阳性表达率为76.0%(19/25),肠化伴不典型增生组织中的阳性表达率为60.4%(29/48),GCA组织中的阳性表达率为36.4%(20/55),比较差异有统计学意义(P<0.05).Villin蛋白的表达与GCA的分化程度有关(P<0.05).结论 Villin蛋白参与了贲门组织早期肠化和GCA的发生,并在GCA的细胞分化中起重要作用.     

Special features of intestinal metaplasia and its relation to early gastric carcinoma in man: observation by a method in which leucine aminopeptidase activity is used.

The degree of intestinal metaplasia and its macroscopic distribution in gastric mucosa were examined by a new method in which leucine aminopeptidase (LAP) activity is used to investigate the relationship between intestinal metaplasia and gastric carcinoma. Since LAP is a specific enzyme of intestinal metaplasia, the area showing positive reaction for this enzyme corresponds strictly with the zone of intestinal metaplasia examined microscopically. Almost all metaplasia was demonstrated by this method. This method was used to examine 40 human gastric carcinomas confined to the mucosa. Gastric mucosa containing differentiated tubular-type carcinoma (60%) was associated with a high degree of metaplasia in comparison with the low degree of metaplasia in poorly differentiated carcinoma (40%). Differentiated tubular-type carcinoma was closely related to intestinal metaplasia. However, all carcinomas arising from the mucosa without intestinal metaplasia (18%) were poorly differentiated. Therefore, gastric carcinomas occurring in Japanese patients are frequently and closely related to intestinal metaplasias.     

Expression of Human Telomerase RNA Is an Early Event of Stomach Carcinogenesis

Expression of human telomerase RNA (hTR) and telomerase activity in gastric cancer and corresponding non-cancerous mucosa were studied. Telomerase activity was detected in 23 (88%) of 26 carcinoma tissues. Although all tumor specimens and non-cancerous mucosa expressed various levels of hTR, 21 (81%) of 26 cases expressed hTR at a higher level in the tumor than that in the corresponding mucosa. All 8 gastric carcinoma cell lines also expressed hTR at high levels. Nine (35%) of 26 non-cancerous mucosa showed telomerase activity and all of them contained intestinal metaplasia. The incidence of telomerase-positive mucosa in grade 2 intestinal metaplasia was significantly higher than that in grade 0 or grade 1 intestinal metaplasia, whereas hTR overexpression was found in grade 0 or grade 1 intestinal metaplasia as well as grade 2 intestinal metaplasia. The degree of Heticobacter pylori infection increased in parallel with the level of hTR expression and telomerase positivity. These results overall suggest that Helicobacter pylori infection may he a strong trigger for hTR overexpression in intestinal metaplasia, and this may lead to telomerase reactivation.     

HGC-1在胃癌中的表达及其与临床病理特征和预后的关系

目的:探讨胃癌患者HGC-1表达情况与临床病理特征及预后间的关系。方法:收集西安交通大学第一附属医院2007年8月-2010年10月所收治的100例胃癌患者的资料及肿瘤组织标本,并选取相应的100例正常黏膜组织及35例胃黏膜肠上皮化生组织作为对照组。采用免疫组织化学法检测三组中HGC-1蛋白表达情况。结果:胃癌组织中HGC-1蛋白表达明显高于正常组织（69.0%和8.0%,P<0.05）;HGC-1蛋白于胃黏膜肠上皮化生组织中表达阳性者为23例,阳性率为65.7%,明显高于正常黏膜中表达阳性者8例,阳性率8.0%,具有统计学差异,P<0.05。HGC-1蛋白表达上调与胃癌组织分化程度及PCNA有统计学意义,P<0.05;而与患者年龄、性别、肿瘤大小和部位、浸润深度、UICC分期、淋巴结转移及远处转移、M分期、脉管浸润无统计学意义,P>0.05。不同胃癌分化和PCNA患者的HGC-1蛋白表达有明显统计学差异。结论:胃癌发生与HGC-1存在关联,同时还可能是临床早期诊断及预后判断的重要指标。     

EXPRESSION OF p16,CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

Gastric carcinoma is one of the most serious diseases in mankind. Its pathogenesis has not been understood very clearly. Recent researches suggested that oncogenes (such as cyclin D1), antioncogenes (ie., p16, Rb) and cell cycle played an important role in the pathogenesis of gastric carcinoma. But there are few reports about the relationship between these genes in gastric carcinoma and gastric premalignant lesions. In this study, we will discuss these problems. MATERIALS AND METHO…     

胃癌组织中肿瘤浸润的免疫细胞NIBP表达与胃癌发生发展的关系

目的:分析胃癌组织中肿瘤浸润的免疫细胞NIBP（NIK and IKKβ binding protein,NIBP）的表达,探讨其与胃癌发生发展的关系。方法:应用免疫组织化学染色法,检测组织芯片中123例胃癌组织肿瘤浸润的免疫细胞和123例相匹配的癌旁良性胃组织上皮细胞间免疫细胞NIBP蛋白的表达水平。结果:胃癌（P=0.012）和萎缩性胃炎伴肠上皮化生（P=0.015）组织中免疫细胞NIBP表达水平明显高于正常胃黏膜和浅表性胃炎。弥漫型胃癌组织中免疫细胞NIBP的表达水平明显高于肠型胃癌（P=0.013）和癌旁良性胃组织（P=0.002）。胃癌组织（P=0.087）及肠型胃癌组织（P=0.860）与癌旁良性胃组织相比,免疫细胞NIBP的表达水平无明显差异。在弥漫型胃癌组织中,肿瘤浸润的免疫细胞NIBP表达水平与淋巴结转移显著相关（P=0.032）,随着淋巴结转移数量增多,肿瘤浸润的免疫细胞NIBP表达水平增高。结论:肿瘤浸润的免疫细胞NIBP表达可能在炎症反应促进胃癌的发生、发展过程中发挥重要作用。NIBP可能是今后胃癌治疗新的分子靶点。     

PTEN基因编码产物与胃癌发生发展相关性的研究

目的 :观察抑癌基因PTEN编码蛋白在正常胃黏膜、肠上皮化生及胃癌组织中的表达 ,探讨PTEN与胃癌发生发展的关系及作用机制。方法 :采用sABC免疫组化方法检测 184例胃癌及其癌旁肠上皮化生组织中PTEN蛋白表达 ,比较其与胃癌的WHO组织学分型、Lauren分型、临床病理分期及淋巴结转移的关系 ;另对其中 6 8例胃癌同时检测血管内皮生长因子 (VEGF)并比较它与PTEN蛋白表达的关系。结果 :胃癌组织PTEN蛋白表达显著低于正常胃黏膜 (47 8%vs 10 0 % ,P <0 0 1)。弥漫型胃癌PTEN表达显著低于肠型胃癌 (41 5 %vs 5 7 8% ,P <0 0 5 ) ;弥漫型胃癌癌旁肠上皮化生组织PTEN蛋白表达显著低于肠型胃癌旁肠化组织 (5 2 5 %vs 10 0 % ,P <0 0 1) ;进展期胃癌PTEN表达显著低于早期胃癌 (40 9%vs 6 7 6 % ,P <0 0 1) ;PTEN蛋白表达降低或失活与胃癌淋巴结转移显著正相关 (转移组4 0 3%vs非转移组 6 3 3% ,P <0 0 1) ;PTEN蛋白与VEGF表达 (31/6 8,4 5 6 %vs 5 1/6 8,75 0 % )呈一定负相关。结论 :PTEN失活或蛋白表达降低与胃癌细胞分化程度、临床病理分期及转移能力密切相关。提示PTEN基因编码产物的检测可作为判定胃癌发生及侵袭转移能力的一项客观指标     

Rsf-1在胃癌和癌前病变组织中的表达及临床意义

目的:染色质重塑因子1(chromatin remodeling factor 1,Rsf-1)可作为肿瘤靶向治疗的靶点,因此探讨其在胃癌(gastric cancer)及癌前病变(precancerous lesions)组织中的表达及临床意义。方法:采用免疫组化SP法检测30例萎缩性胃炎、30例肠上皮化生、22例不典型增生Rsf-1蛋白表达水平。并检测64例胃癌与配对癌旁组织(手术切缘距离肿瘤>5 cm)中Rsf-1和p53蛋白表达水平并分别分析与胃癌临床病理参数间的关系,同时分析Rsf-1与p53在胃癌中表达的相关性。结果:Rsf-1在胃癌、肠上皮化生、不典型增生组织中的阳性表达率均高于癌旁组织(P＜0.05)。Rsf-1在胃癌中表达与淋巴结转移有关(P＜0.05）。p53在胃癌中的阳性表达率高于癌旁组织,其表达与淋巴结转移有关(P＜0.05)。p53和Rsf-1在胃癌中的表达存在正相关性(r=0.38,P＜0.05),两者在胃癌中共阳性表达与淋巴结转移有关（P＜0.05)。结论:Rsf-1可能参与了胃癌病变的发生及发展,对胃癌早期筛查具有重要指导意义。Rsf-1和p53两者共阳性表达对于预测胃癌淋巴结转移可能具有一定的参考价值。     

Atrophic gastritis, Epstein–Barr virus infection, and Epstein–Barr virus-associated gastric carcinoma

Background. The developmental process of Epstein–Barr virus (EBV)-associated gastric carcinoma (EBVaGC) has not been clearly demonstrated, especially in its relation to intestinal metaplasia and epithelial EBV infection. Methods. Gastritis and intestinal metaplasia was histologically evaluated in non-neoplastic gastric mucosa that surrounded early carcinoma of EBVaGCs (n = 23) and EBV-negative gastric carcinomas (GCs) (intestinal type, n = 139; diffuse type, n = 44). Helicobacter pylori infection was evaluated by immunohistochemistry. EBV infection in the gastric mucosa was examined by both RNA probe in situ hybridization (ISH) and polymerase chain reaction (PCR) for the BamHI-W region of EBV DNA, the latter of which was applied to the microdissected mucosa. Results. Marked grade of atrophy and moderate to marked grade of lymphocytic infiltration were significantly more frequent in EBVaGCs (74% and 78%, respectively), compared to intestinal-type (49% and 12%)and diffuse-type (27% and 12%) of EBV-negative GCs. Only 13% of EBVaGCs were surrounded by intestinal metaplasia, in contrast to 41% of intestinal-type EBV-negative GCs. Immunohistochemistry revealed nearly the same frequencies of H. pylori infection (70%) in three types of GCs. RNA probe ISH for EBV-DNA failed to identify any positive cells in nonneoplastic mucosa, including intestinal metaplasia. Two of 118 microdissected samples of EBVaGC and 5 of 62 samples of EBV-negative GCs showed amplification of EBV-DNA, consisting of 3 pyloric and 4 fundic but no metaplastic gland samples. Conclusions. EBVaGC may develop from rare EBV-infected epithelial cells with severe atrophic gastritis, but the process is not directly related to intestinal metaplasia or H. pylori infection. Received for publication on Sept. 22, 1998; accepted on April 27, 1999