单克隆抗体MG7在胃癌癌前病变组织中的免疫组织化学研究

作者应用胃癌单克隆抗体MG7对289例胃粘膜活检标本进行PAP免疫组织化学观察,发现伴有肠化生的萎缩性胃炎组(20.0％)与伴有肠化生的癌旁粘膜组(62.1％)间、弥漫型胃癌癌旁粘膜肠化生组(41.7％)与肠型胃癌癌旁粘膜肠化生组(76.5％)间、轻型不典型增生组(23.9％)与中重度不典型增生组(54.0％)间,MG7-Ag表达阳性率均有显著性差异(均为P<0.01)。在胃癌组织中MG7-Ag表达阳性率为87.8％,而8例正常胃粘膜均阴性。结果表明,胃癌单克隆抗体MG7对胃癌的诊断具有较高的特异性;肠化生与胃癌(尤其是肠型胃癌)的发生有密切关系;对MG7-Ag表达阳性的肠化生和异型增生患者加强随访,将有利于胃癌的早期发现。     

胃粘膜肠上皮化生CEA的免疫组织化学研究

用PAP法对84例胃粘膜肠化上皮癌胚抗原(CEA)作了光镜和免疫电镜观察。癌旁肠化CEA阳性率(80.60%)和硫酸粘液阳性率(97.01%)均明显高于胃良性病变伴肠化(47.06%,29.41%);硫酸粘液(+)组肠化CEA阳性率(81.43%)明显高于硫酸粘液(一)组(35.71%)。产生CEA胃癌的粘液与结肠粘液类似,而不产生CEA胃癌的粘液与胃粘液类似。文中还对肠化与胃癌的关系及胃癌的组织发生进行了讨论。     

胃癌组织细胞外信号调节激酶1/2表达及其与幽门螺杆菌关系的初步分析

目的探讨胃癌发生、发展过程中细胞外信号调节激酶1/2(extracellular signal regulated kinase 1/2,ERK1/2)表达及其与幽门螺杆菌(Helicobacter pylori,HP)的关系。方法采用免疫组化SP两步法对比观察单纯性胃炎(20例)、胃黏膜上皮肠上皮化生(肠化)(20例)、不典型增生(28例)、早期胃癌(36例)、进展期胃癌(73例)中HP、ERK1/2、蛋白激酶Cθ(Protein kinase Cθ,PKCθ)的表达。结果不典型增生组(39.29%)和肠化组(30.00%)HP检出率均明显高于单纯胃炎组(5.00%)、早期胃癌组(2.78%)和进展期胃癌组(1.39%)(P0.05)。单纯胃炎组、肠化组和不典型增生组ERK1/2染色阴性;早期胃癌组(63.88%)和进展期胃癌组(68.49%)癌细胞呈ERK1/2阳性着色。低分化腺癌组(82.50%)ERK1/2表达明显高于高分化腺癌组(51.52%)(P0.05)。对各组标本进行PKCθ免疫组化染色后,发现PKCθ仅在早期胃癌和进展期胃癌的间质及癌周淋巴细胞中阳性着色。高分化腺癌组PKCθ表达(54.55%)明显高于低分化腺癌组(32.50%)(P0.05)。结论 HP感染导致慢性胃炎、肠化、不典型增生。在胃癌的发生、发展过程中可能涉及ERK1/2的高表达。PKCθ在胃癌中的意义尚需进一步研究。     

胃癌及癌前病变的血型物质

血型物质或称A.B.H同族抗原,在各种正常组织和细胞中常具有一定的分布。当细胞发生去分化或癌变时,(包括胃癌),细胞内血型物质常呈现消失或减少,因此,有些作者试图应用血型物质作为肿瘤恶性度的指标。但到目前为止,对不同组织学类型的胃癌的血型物质消长情况;以及对胃粘膜不典型上皮增生及肠化生的血型物质变化的情况,均尚无详细的研究。本文的目的是研究胃癌的不同的组织学类型及癌前病变的血型物质的消长变化并分析其意义。材料和方法收集82例外科切除的带癌胃标本及33例具有不典型增生(其中24例伴有肠化生改变)的胃标本。采用Alcian Blue(AB)pH2.5及AB/PAS染色以显示酸性及中性粘蛋白。采用特异性红细胞粘附试验     

不同组织类型胃癌间质淋巴细胞免疫组织化学研究

不同组织类型胃癌间质淋巴细胞免疫组织化学研究杨关虎，徐天蓉，徐旭东，刘玉龙，郑肇巽一、材料与方法选择资料完整的分化性腺癌、粘液腺癌、粘液细胞癌和低分化腺癌各５例，用原蜡块作ＡＢＣ法免疫标记，按癌内、癌旁和癌外间质三个区域，对ＨＥ切片观察淋巴细胞和浆细...     

胃癌碱性磷酸酶同工酶组织化学,光镜和电镜观察

采用光间和电镜酶组织化学技术对胃癌和胃良性病变碱性磷酸酶同工酶的活性和分布进行观察，结果表明：Ｎａｇａｏ，Ｒｅｇａｎ和Ｋａｓａｈａｒａ同工酶在正常胃粘膜和非癌病变中均无表达，可作为胃癌的肿瘤标志；肠化上皮仅表达小肠型ＡＬＰ，是肠化上皮分化成熟的标志。从ＡＬＰ同工酶基因表达角度来看，两次突变假说和隐性基因突变假和说适用于胃癌。     

胃癌MG7抗原与其组织发生关系的研究

应用我国研制的胃癌单克隆抗体MG7的免疫组化及粘液组化技术对193例胃组织中MG7-Ag及粘液分布进行了规察。胃癌组织MG7-Ag阳性率为87.8％,癌旁肠化硫酸粘液(+)检出率62.1％高于慢性胃炎伴肠化组织(33.7％)(P<0.005);硫酸粘液(+)组肠化MG7-Ag检出率(47.1％)高于硫酸粘液(-)组肠化(25.9％)(P<0.01),肠型胃癌MG7-Ag阳性率(100.0％)高于胃型(66.7％)和干细胞型(77.8％)(P<0.005),硫酸粘液(+)组胃癌MG7-Ag阳性率(100.0％)高于硫酸粘液(-)组胃癌(81.9％)(P<0.01)。提示产生MG7-Ag胃癌的发生可能与含硫酸粘液的结肠型肠化有关,而不产生MG7-Ag的胃癌可能来自胃固有粘膜。     

胃癌中LIMK1的表达及其病理意义

目的 探讨LIMK1在胃癌中的表达及其临床病理意义.方法 应用组织芯片与免疫组织化学SP法检测81例胃癌、26例不典型增生及34例正常组织中LIMK1的表达水平,分析其与胃癌临床分期、有无淋巴结转移等临床病理特征的关系.结果 LIMK1在正常组织、不典型增生与胃癌中表达呈递增趋势(P<0.05);弥漫型胃癌阳性率明显高于肠型胃癌(P<0.05).肿瘤直径≤3.0 cm的胃癌中LIMK1的表达明显低于＞3.0 cm的表达(P<0.05);淋巴结转移组表达明显高于未转移组(P<0.05).TNM分期Ⅲ、Ⅳ期表达明显高于Ⅰ、Ⅱ期(P<0.05);LIMK1表达与患者性别差异无显著性(P>0.05).结论 LIMK1与胃癌的分化程度、肿瘤大小、淋巴结转移、临床分期密切相关,可能是胃癌侵袭转移重要的生物标记物.     

胃癌癌前病变的探讨——萎缩性胃炎、肠上皮化生及非典型增生与胃癌的关系

以胃癌和胃、十二指肠溃疡手术标本为材料,用组织形态学和组织化学法,对萎缩性胃炎、肠化及非典型增生与胃癌发生的关系进行了探讨。作者根据结果认为:单纯的萎缩性胃炎和不伴异型增生的肠化与胃癌的组织发生可能无直接关系,而在慢性萎缩性胃炎和肠化基础上发生的中、重度非典型增生则可能是胃癌发生的组织学基础。     

Ezrin和CD44v6在胃癌中的表达及其临床意义

目的 探讨胃癌组织中Ezrin和CD44v6的表达及其临床病理意义.方法 应用免疫组织化学(SP法)检测73例胃腺癌患者组织标本、15例胃不典型增生组织及12例癌旁胃黏膜组织中Ezrin和CD44v6的表达情况.结果 (1)Ezrin 在正常胃黏膜组、胃不典型增生组和胃癌组中的阳性表达率分别为41.7%、53.3%和83.6%.CD44v6在正常胃黏膜组、胃不典型增生组和胃癌组中的阳性表达率分别为25%、40%和82.2%.(2)Ezrin和CD44v6的表达与淋巴结转移密切相关,有淋巴结转移组Ezrin与CD44v6的阳性率均明显高于无淋巴结转移组(P<0.05);在Ezrin和CD44v6同时表达组中,淋巴结转移率为63%(34/54例)高于两者均为阴性组(1/6例,16.7%)(P＜0.05).结论 联合检测Ezrin和CD44v6的表达有助于预测胃癌的恶性程度和转移潜能.     

Histopathological phenotypes of early gastric cancer and its background mucosa

Recent advances in endoscopic submucosal dissection (ESD) techniques contribute to endoscopic treatment of early gastric cancer (EGC). Recognition of chronic atrophic gastritis as the background is important for high-quality detection and diagnosis of EGC. But, relationships between EGC and atrophy of the background gastric mucosa caused by Helicobacter pylori are not well understood. The present study demonstrated histopathological phenotypes of EGC, as well as chronic atrophic gastritis as background mucosa of EGC. We evaluated mucosal heights, number of glands, and degree of intestinal metaplasia (IM) of the background gastric mucosa, using 81 cases of EGC resected by ESD. Gastric phenotype cancer cases showed IM of the background gastric mucosa less frequently, compared with intestinal phenotype cancer cases (score of IM, 1.15 vs. 1.65, P = 0.012). The average mucosal heights around EGC were lower in moderately to poorly differentiated adenocarcinoma cases than well differentiated adenocarcinoma cases (442.6 μm vs. 500.2 μm, P = 0.011). The mucosal atrophy indicated by average heights of background mucosa was low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancercases (452.8 μm vs. 505.6 μm, P = 0.018). In the fundic gland area, the mucosal heights were low in the gastric phenotype cancer cases, compared with the intestinal phenotype cancer cases (413.2 μm vs. 495.5 μm, P = 0.015). Our results using EGC specimens indicated that gastric phenotype cancer and moderately to poorly differentiated adenocarcinoma had atrophic background mucosa with lower mucosal heights and less IM. The atrophic gastric mucosa with less IM is thought to play an important role in gastric carcinogenesis, especially tumoriogenesis of gastricphenotype cancer.     

Features of gastritis predisposing to gastric adenoma and early gastric cancer

BACKGROUND/AIMS: Helicobacter pylori gastritis is a risk factor for the development of gastric cancer. The results of several studies indicate that gastric adenomas, which are considered premalignant lesions, may also be associated with H pylori gastritis. However, it is not clear whether there are different patterns of gastritis in these patients compared with patients with gastric cancer or patients with H pylori gastritis alone. Therefore, this study was designed to investigate the patterns of gastritis in these three groups of patients. METHODS: The histological features of gastric mucosa at a distance from the tumour were analysed prospectively in 118 patients with gastric adenoma (mean age, 71.8; female to male ratio, 6 : 4). In addition, for every patient with H pylori associated gastric adenoma an age and sex matched control patient with either H pylori associated early gastric cancer of the intestinal type or H pylori gastritis only was investigated. RESULTS: Only 60 patients (50.9%) with gastric adenoma were infected with H pylori. In the remaining patients, complete atrophic gastritis predominated. In those patients with adenoma and H pylori infection, the gastritis was similar to that seen in patients with early gastric cancer (median score, 2 for activity and degree of gastritis in the antrum and corpus); intestinal metaplasia was common to both groups. These two groups differed significantly from patients with H pylori gastritis only (median grade and activity of gastritis, 1 in antrum and corpus), in whom intestinal metaplasia was rare. CONCLUSIONS: It appears that gastric adenomas and gastric intestinal cancer arise by analogous mechanisms. However, owing to severe atrophic gastritis and a lower incidence of H pylori, adenomas do not appear to be definite precursor lesions for gastric cancer.     

The phenotype of gastric mucosa coexisting with Barrett's oesophagus

BACKGROUND/AIMS: Barrett's oesophagus complicates the gastro-oesophageal acid reflux. Helicobacter pylori infection, particularly with cagA positive strains, induces inflammatory/atrophic lesions of the gastric mucosa, which may impair acid output. No systematic study has investigated the phenotype of the gastric mucosa coexisting with Barrett's oesophagus. This study was designed to identify the phenotype of gastric mucosa associated with Barrett's oesophagus. METHODS: In this retrospective case control study, the phenotype of the gastric mucosa was histologically characterised in 53 consecutive patients with Barrett's oesophagus and in 53 (sex and age matched) non-ulcer dyspeptic controls. Both patients and controls underwent extensive sampling of the gastric mucosa (two antral, one incisural, and two oxyntic biopsies). Intestinal metaplasia (IM) was categorised (type I, complete IM; types II and III, incomplete IM) by the high iron diamine stain; cagA status was ascertained by genotyping. RESULTS: Helicobacter pylori was present in 19 of the 53 patients with Barrett's oesophagus and in 30 of the 53 controls (p < 0.02); eight of the 19 patients with Barrett's oesophagus and 28 of the 35 controls harboured cagA positive H pylori (p < 0.03). The histological severity of non-atrophic gastritis detected in the controls was significantly higher than that detected in the patients with Barrett's oesophagus (p < 0.0001). Multifocal atrophic gastritis was present in 4% of the patients with Barrett's oesophagus and in 23% of controls (p < 0.01). The odds ratio for the association between multifocal atrophic gastritis and Barrett's oesophagus was 0.20 (95% confidence interval, 0.006 to 0.60). Gastric IM was detected in 13.2% of the patients with Barrett's oesophagus and in 30.1% of the controls (p < 0.03). Type III IM at the gastric mucosa was only detected among controls. CONCLUSIONS: Barrett's oesophagus is associated with a low prevalence of H pylori cagA positive infection and multifocal atrophic gastritis. This pathobiological pattern is considered to be associated with a low risk of distal gastric cancer.     

Immunohistological study of the normal human gastric mucosa and that of chronic gastritis

Normal gastric mucosa and that in atrophic gastritis was studied by indirect immunoperoxidase method. Intestinal antigens CEA and beta 1MA were found in the foetal stomach and in the foci of intestinal metaplasia with and without dysplastic epithelial changes. Gastric antigens, pepsinogens of the foetal and 2-nd type, were found in foetal and adult stomach, as well as in the foci of intestinal metaplasia with dysplastic changes. The discovery of concomitant presence of gastric and colonic antigens in the dysplastic epithelium may indicate the existence of pluripotent stem cells capable of differentiation in the direction of gastric glandular epithelium, and in the direction of enterocytes. The possibility is suggested of origination of gastric carcinoma of different histologic structure from intestinal metaplasia with dysplastic changes.     

MUC1 gene polymorphism in the gastric carcinogenesis pathway.

MUC1 like most mucin genes shows extensive length polymorphism in the central core region. In a previous study it was shown that individuals with small MUC1 alleles/genotypes have an increased risk for development of gastric carcinoma. Our aim was to see if MUC1 gene polymorphism was involved in susceptibility for the development of conditions that precede gastric carcinoma: chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). We evaluated MUC1 polymorphism in a population of 174 individuals with chronic gastritis (CG) displaying (CAG) and/or intestinal metaplasia (IM). The population of patients with CG shows MUC1 allele frequencies significantly different from the gastric carcinoma patients and blood donors population. A significantly lower frequency of CAG and IM was observed in MUC1 VNTR heterozygotic patients. Within the group of patients with IM, MUC1 large VNTR homozygotes show a significantly higher frequency of complete IM while small VNTR homozygotes show a significantly higher frequency of incomplete IM. These findings show that MUC1 polymorphism may define different susceptibility backgrounds for the development of conditions that precede gastric carcinoma: chronic atrophic gastritis (CAG) and intestinal metaplasia (IM).     

Early gastric cancer. Clinico-pathological analysis of 125 cases of early gastric cancer (EGC)

The frequency and the pathological findings of 125 early gastric cancers (ECGs), and particularly of small and minute lesions, were evaluated in a retrospective study of 839 surgical specimens of gastric carcinoma. Sixty two ECGs were believed to have risen from gastric epithelium, 27 from areas of intestinal metaplasia, and 3 from cardio-pyloric mucosa. The remaining lesions showed mixed histological patterns. The most frequent macroscopic type was IIc (24.8%) followed by IIb (16.8%), I (16.8%), and III (14.4%). In 63 cases (50.4%) the cancer was limited to the mucosa. In all specimens, and particularly in small and minute lesions, the surrounding mucosa was accurately analyzed to detect any lesions, from which the cancer could have developed. Intestinal ECGs, especially if protruded, seem to arise from areas of intestinal metaplasia or of chronic atrophic gastritis. Rarely ECGs seem to stem from polypoid lesions both hyperplastic and adenomatous. On the contrary, most important seems to be the role of ulcerative lesions, since in 14 cases of our series, carcinomatous foci were observed within the regenerative epithelium covering the crater. No correlation was found between histologic type, size, staging, and frequency of node metastasis; this suggests the existence of ECGs with different biologic behaviour.     

Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis

Gastric cancers are commonly subdivided into intestinal and diffuse subtypes on a morphologic basis, supported by corollary evidence of differences at the pathogenetic and molecular levels. Chronic atrophic gastritis with intestinal metaplasia is a common precursor lesion for the intestinal type of carcinoma. To identify early molecular changes, in this study we have examined 13 surgical specimens both for the expression of E-cadherin, p53 and beta-catenin by immunohistochemistry and for methylation of the CDH1 promoter (E-cadherin) by bisulfite genomic sequencing of laser capture microdissected samples. Each specimen examined contained areas of normal (nonmetaplastic) gastric mucosa, as well as areas of intestinal metaplasia and/or carcinoma. Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDH1 promoter were observed in all of the metaplasia samples. Thus, the methylation status of the CDH1 promoter and expression of E-cadherin together provide strong evidence that loss of E-cadherin is an early event in intestinal type gastric carcinogenesis. In contrast, expression of p53, assumed to be mutant p53, was generally not detected (except for isolated cells) until the carcinoma stage in tissues from these patients. These results suggest that mutation of p53 is a late event in intestinal type gastric cancer. The level of beta-catenin expression did not appear to change between normal, metaplastic and carcinoma cells of intestinal type, and no nuclear staining was visible in any of the tissues. These results suggest that the Wnt signaling pathway is not upregulated in this type of cancer.     

c-met蛋白表达与胃粘膜病变的关系及预后意义

目的 研究ｃ－ｍｅｔ蛋白在胃粘膜病变演进过程中的表达及关系,探讨ｃ－ｍｅｔ表达对胃癌预后的意义。方法 对１６９例经病理证实的不同胃粘膜病变采用免疫组织化学ＳＰ法检测ｃ－ｍｅｔ蛋白表达,用Ｋａｐｌａｎ－Ｍｅｉｅｒ法的Ｌｏｇ－ｒａｎｋ检验胃癌生存率。结果 在浅表性胃炎、萎缩性胃炎、肠化生、异型增生、早期胃癌和进展期胃癌中,ｃ－ｍｅｔ蛋白表达率分别为２３．５％（４／１７）,３６．８％（１４／３８）,５１．５％（１７／３３）,６１．３％（１９／３１）,６６．７％（８／１２）和７３．７％（２８／３８）,而且肠化生、异型增生、胃癌均显著高于浅表性胃炎（Ｐ〈０．０５）。胃粘膜增殖程度与ｃ－ｍｅｔ阳性表达强度密切关系分析,两者有显著关联（Ｐ〈０．０１）。ｃ－ｍｅｔ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Ｂｏｒ