食管癌癌变过程中端粒DNA长度与细胞DNA含量的变化及意义

目的 探讨在食管癌癌变过程中端粒DNA长度和细胞DNA含量的变化及意义.方法 采用流式细胞术荧光原位杂交、碘化丙啶DNA荧光染色法定量检测100例食管上皮脱落细胞(其中食管上皮正常18例,轻度增生16例,重度增生35例,癌31例)中端粒DNA长度、细胞内DNA含量和细胞周期分布.结果 流式细胞术荧光原位杂交检测各组的端粒长度,Q-FISH值分别为正常组(50.83±8.86)、轻度增生(49.51±3.16)、重度增生(36.96±8.02)和癌组(27.81±6.59);癌组端粒长度明显短于重度增生组、轻度增生和正常组(P<0.01),同时重度增生组短于轻度增生组和正常组(P<0.01);端粒DNA长度Q-FISH值与细胞学分级呈显著负相关(r=-0.79,P<0.01).正常组、轻度增生组、重度增生组和癌组细胞中DNA指数(DI)分别为(1.01±0.32)、(1.04±0.21)、(1.10±0.28)和(1.51±0.36),正常组、轻度增生组和重度增生组的DI值相比,差异无显著性意义,而癌组的DI值明显高于其他三组;DI值与细胞学分级呈显著正相关(r=0.60,P<0.01).端粒长度Q-FISH值与DI值呈显著负相关(r=-0.46,P<0.01).结论 端粒DNA长度缩短、细胞DNA含量升高可能参与了食管上皮的癌变过程.     

残胃黏膜DNA增生及细胞动力学变化

着重探讨吻合口与残胃体的细胞动力学变化及细胞ＤＮＡ含量 ,以期作出癌前病变的早期诊断。一、材料和方法1.病例资料 :1997年 2月～ 11月间因残胃复查就诊于山西医科大学第一医院的门诊患者 31例 ,均为行胃部分切除术后 5年以上者。其中男 2 7例 ,女 4例 ,平均年龄 (5 5 .94± 12 .0 5 )岁 ,残胃术后平均时间 (16 .30± 3.73)年。所有患者行胃镜检查 (ＯｌｙｍｐｕｓＧＩＦ ＸＱ2 0 0 型 ) ,并在吻合口及残胃体大弯侧分别取活检 8块 ,其中 3块行流式细胞仪 (ＦＣＭ )检测 ,其余做病理检查。2 .ＤＮＡ含量及细胞动力学检测 :①ＤＮＡ含量 :…     

胃黏膜癌变过程中环氧合酶-2表达及其意义

流行病学调查显示,长期服用非甾体类抗炎药(NSAIDs)的人群发生大肠癌的危险性可降低40％～50％。在结肠癌、乳腺癌、胰腺癌等肿瘤动物模型复制过程中,长时间加用NSAIDs可明显降低肿瘤的发生率。NSAIDs作用的中心环节是抑制环氧合酶(COX)的活性,而     

不同病变胃粘膜的端粒长度与细胞内DNA含量

目的分析不同病变胃粘膜细胞内端粒长度的差异,以及细胞内DNA的含量,并探讨端粒行为异常、细胞内DNA含量与胃粘膜癌变的关系.方法对172例内镜活检和45例胃癌手术标本,应用Southern杂交分析细胞内端粒长度,应用流式细胞术测定细胞内DNA含量.结果在172例内镜活检标本中,正常胃粘膜,慢性浅表性胃炎,伴0,1,2度肠化的慢性萎缩性胃炎和胃癌组织的端粒长度分别是10.4Kb±0.2Kb,9.9Kb±0.4Kb,9.8Kb±1.2Kb,8.6Kb±1.0Kb,6.2Kb±1.2Kb,5.9Kb±2.6Kb.在45例胃癌手术标本中结果相似.流式细胞术分析细胞内DNA含量的结果是,在门诊内镜活检标本中,正常胃粘膜,慢性浅表性胃炎,伴0,1,2度肠化的慢性萎缩性胃炎和胃癌组织的异倍体DNA检出率分别为0.00%,0.00%,0.00%,10.00%,12.50%,33.33%.在45例胃癌手术切除标本中结果也相似.而且异倍体细胞内的端粒长度明显短于二倍体细胞内的端粒长度,同时异倍体细胞中的端粒长度与DNA指数呈负相关(r=-0.91,P＜0.01),也就是端粒越短DNA指数越高.结论端粒长度从正常胃粘膜、不同程度肠化胃粘膜到癌变胃粘膜而逐渐缩短.在正常胃粘膜和慢性浅表性胃炎中未检出异倍体DNA,从1度肠化、2度肠化到癌变的胃粘膜异倍体DNA检出率逐渐增高,而且在异倍体细胞中端粒长度和DNA指数呈负相关,推测可能存在端粒愈短DNA扩增愈活跃的情况,端粒缩短伴有DNA指数增加可能是胃癌发生的预兆.     

胃黏膜细胞线粒体DNA不稳定及核内整合与幽门螺杆菌感染有关

目的：线粒体DNA（mtDNA）因缺乏组蛋白保护，且损伤修复系统不健全，容易为幽门螺杆菌（Hp）相关胃炎中氧自由基的重要靶点，为此探讨胃黏膜细胞线粒体DNA不稳及核内整合与Hp感染的关系。方法：采用PCR和Giemsa染色检测Hp；采用限制性片段多态性（PCR－SSCP）和原位杂交方法检测胃黏膜细胞线粒体DNA微卫星不稳定（mtMSI）及核内mtDNA序列。结果：30例胃癌检出mtMSI11例（36．7％），15例肠化中有2例（13．3％），10例异型增生中有2例，10例萎缩性胃炎中有1例检出mtMSI。胃癌细胞核内mtDNA序列的检出率为20．0％（6／30），异型增生为1／10例，肠上皮化生为6．7％（1／15），萎缩性胃炎为1／10例，胃黏膜细胞mtMSI及核内mtDNA序列的检出率在Hp感染组（12／39，8／39）显著高于非Hp感染组（4／36，1／36，P＜0．05）。虽cagA^ 组mtMSI及核内mtDNA序列检出率（10／25，6／25）高于cagA^-组（2／14，2／14），但两组mtMSI及核内mtDNA序列检出率比较，差异并无显著性（P＞0．05）。结论：胃黏膜细胞mtMSI及mtDNA序列核内整合可能与Hp感染有关，并参与胃癌的发生。     

胃黏膜癌变过程中增殖诱导配体及其受体表达水平分析

目的 分析胃癌发生各阶段组织中增殖诱导配体（APRIL）及其受体mRNA的表达水平。方法 在APRIL及其受体基因的高保守区设计相应引物和荧光探针，实时检测PCR产物的荧光强度，根据标准品建立标准曲线，由软件自动计算出待测样本中靶基因mRNA的准确含量，并以靶基因和内参β2微球蛋白（β2M）mRNA含量比值作为评价靶基因表达水平的指标。结果 采用实时荧光定量PCR（RFQ-PCR）检测靶基因mRNA含量的线性范围为10^1～10^9pg／ml，批内和批间重复性测定的变异系数（d）分别为6．52％～12．02％和8．76％～14．16％。APRIL在肠上皮化生、异型增生和胃癌组织中的表达水平显著高于正常胃黏膜（P〈0．05）．在胃癌组织中的表达水平又显著高于肠上皮化生和异型增生（P〈0．05），而其受体B细胞成熟抗原（BCMA）和穿膜蛋白活化物（TACI）在各种胃黏膜病变之间表达水平差异无统计学意义（P〉0．05）。结论 RFQ-PCR检测APRIL及其受体mRNA含量，具有较好的灵敏度和重复性。APRIL在胃癌病变演进过程中呈现累积和渐进趋势，可能在胃癌发生、发展过程中起重要作用．有可能成为胃癌早期诊断和抗癌治疗的靶分子。肿瘤组织可能还表达APRIL未知受体。     

胃黏膜肠上皮化生、胃上皮内瘤变与胃癌的组织发生

胃癌是严重危害人民健康的疾病之一,其发病机制尚不明确.胃癌的发生常在癌变之前经历相当漫长的演变过程,即由正常胃黏膜转变成胃癌前病变,部分再发展成胃癌.目前公认,胃黏膜异型增生和肠上皮化生是胃癌前病变.鉴于胃癌的高度恶性,且其病因发病机制尚未完全阐明,实施针对病因的一级预防比较困难.本文就胃上皮内瘤变、异型增生和肠化生的定义和分类,幽门螺杆菌感染、萎缩性胃炎、肠化生与胃癌发生的相关性等问题进行综述,旨在提高对胃癌前病变的认识水平,以便于临床医师对胃癌前病变、特别是萎缩性胃炎进行密切的监测及予以及时有效的干预.     

Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients

AIM: To compare Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients in different age groups and from different biopsy sites. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of gastric ulcer and chronic gastritis patients. Giemsa staining, improved Toluidine-blue staining and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of activity of H pylori infection, mucosal inflammation, glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: Total rate of H pylori infection, mucosal inflammation, activity of H pylori infection, glandular atrophy and intestinal metaplasia in 3 839 gastric ulcer patients (78.5%, 97.4%, 82.1%, 61.1% and 64.2%, respectively) were significantly higher than those in 4 102 chronic gastritis patients (55.0%, 90.3%, 56.2%, 36.8%, and 37.0%, respectively, P<0.05). The rate of H pylori colonization of chronic gastritis in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 33.3%, 41.7%, 53.6%, 57.3%, 50.7%, 43.5%, respectively; in corpus, it was 32.6%, 41.9%, 53.8%, 60.2%, 58.0%, 54.8%, respectively; in angulus, it was 32.4%, 42.1%, 51.6%, 54.5%, 49.7%, 43.5%, respectively. The rate of H pylori colonization of gastric ulcer in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 60.5%, 79.9%, 80.9%, 66.8%, 59.6%, 45.6%, respectively; in corpus, it was 59.7%, 79.6%, 83.6%, 80.1%, 70.6%, 59.1%, respectively; in angulus, it was 61.3%, 77.8%, 75.3%, 68.8%, 59.7%, 45.8%, respectively. The rate of H pylori colonization at antrum was similar to corpus and angulus in patients, below 50 years, with chronic gastritis and in patients, below 40 years, with gastric ulcer. In the other age- groups, the rate of H pylori colonization was highest in corpus, lower in antrum and lowest in angulus (all P<0.05). The rates of glandular atrophy and intestinal metaplasia were higher and earlier in H pylori-positive patients than those without H pylori infection (both P<0.01). In comparison of gastric ulcer patients with chronic gastritis patients, the rate of glandular atrophy and intestinal metaplasia was higher in H pylori-positive patients with gastric ulcer than in H pylori-positive patients with chronic gastritis (both P<0.01); the rate of glandular atrophy and intestinal metaplasia were also higher in H pylori-negative patients with gastric ulcer than in H pylori-negative patients with chronic gastritis (both P<0.01). Both glandular atrophy and intestinal metaplasia were much more commonly identified in the angulus than in the antrum, lowest in corpus (all P<0.01). CONCLUSION: Rate of H pylori infection, glandular atrophy and intestinal metaplasia in gastric ulcer were higher than in chronic gastritis in all-different age -groups. Distribution of H pylori colonization is pangastric in the younger patients. It is highest in corpus, lower in antrum and lowest in angulus in the older age groups. Progression of glandular atrophy and intestinal metaplasia seem to have a key role in the distribution of H pylori colonization. H pylori appears to be the most important risk factor for the development of glandular atrophy and intestinal metaplasia, but it is not the only risk.     

胃癌癌变过程中Smad4表达的变化及其与临床病理特征的关系

目的:探讨胃癌癌变过程中Smad4蛋白的表达变化及其与临床病理特征的关系.方法:利用组织病理学和免疫组织化学的方法,对103例胃癌患者(早期16例,进展期87例)的石蜡标本进行了病理学分类,并检测各级病变中Smad4蛋白的表达情况.结果:其中在28例标本中同时检出肠上皮化生,在13例标本中检出不典型增生,有2例标本同时检出肠上皮化生和不典型增生.癌旁的正常胃黏膜细胞均有Smad4蛋白表达,在肠上皮化生和不典型增生中表达阳性率分别为89.3%和76.9%.在癌细胞中则为54.4%,其中早期癌为62.5%,进展期癌为52.9%.随着恶变程度的增加,Smad4蛋白表达下降的频率显著升高(P<0.05).Smad4蛋白表达与癌细胞的分化程度密切相关(P<0.01),低分化癌细胞中Smad4蛋白表达下降的频率更高,为63.0%,而高分化癌细胞中Smad4蛋白表达下降的频率仅为31.6%.贲门部癌Smad4蛋白的表达阳性率明显高于其他部位(P<0.05),为75%.胃底、胃体和胃窦部癌的表达阳性率基本相似,分别为50%,53.6%和46.7%.Smad4蛋白表达与患者年龄、性别、肿瘤大小、淋巴结转移、浸润深度未见明显相关性.结论:Smad4蛋白表达下降是胃癌癌变过程中频发的分子事件,并且与细胞恶变的进展程度和分化程度密切相关,但在贲门部癌中表达下降的频率较低.     

Latest insights into the effects of Helicobacter pylori infection on gastric carcinogenesis

There appears to be the strong association between Helicobacter pylori (H pylori) and gastric cancer. We reviewed the latest evidences about the effects of H pylori infection on gastric carcinogenesis, classified into epidemiology, dynamics of gastric mucosal changes, DNA damages, virulence factors, host factors, and source of gastric malignancy. Through the considerable progress made in research into virulence factors resulting from differences between H pylori strains, such as cagA positivity, as well as into host factors, such as gene polymorphisms, a diverse spectrum of H pylori-associated diseases, including gastric cancer, is beginning to lend itself to elucidation. The impact of the novel hypothesis advanced by Houghton et al proposing bone-marrow derived stem cells (BMDC) as a potential source of gastric malignancy on evolving research remains to be seen with interest. Further progress in research into H pylori eradication as a viable prophylaxis of gastric cancer, as well as into the mechanisms of gastric carcinogenesis, is to be eagerly awaited for the current year and beyond.     

Apoptotic cell death and its relationship to gastric carcinogenesis

AIM: To investigate the apoptotic process of cells with in the intestinal metaplasia areas co-localizing with chronic gastritis and gastric carcinomas and to analyze the involvement of proteins regulating apoptosis in the process of intestinal metaplasia related gastric carcinogenesis. METHODS: Forty-two gastric carcinoma and seventeen chronic gastritis cases were included in this study. All cases were examined for the existence of intestinal metaplasia. Ten cases randomly selected from each group were processed for TUNEL assay. TUNEL positive cells within the intestinal metaplasia areas, co-localizing either to gastric carcinoma or chronic gastritis, were counted and converted to apoptotic indices. In addition, p53, bcl-2 and bax expression patterns within these tissues were analyzed on the basis of immunohistochemistry. RESULTS: Twenty-eight of the cases were intestinal and 14 of the cases were diffuse type adenocarcinomas. 64% (27/42) of the gastric carcinoma cases had intestinal metaplasia. Intestinal metaplasia co-localized more with intestinal type carcinomas compared with diffuse type carcinomas [75% (21/28) vs 42% (6/14), respectively; P ≤0.05]. The mean apoptotic index in tumor cells was 0.70±0.08. The mean apoptotic index in intestinal metaplasias co-localizing to tumors was significantly higher than that of intestinal metaplasias co-localizing to chronic gastritis (0.70±0.03 vs 0.09±0.01, respectively; P≤0.05). p53 positivity was not observed in areas of intestinal metaplasia adjacent to tumors or chronic gastritis. Intestinal metaplasia areas adjacent to tumors showed lower cytoplasmic bcl-2 positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [55.5% (15/27) vs 70.5% (12/17), respectively]. On the other hand, intestinal metaplasia areas adjacent to tumors showed significantly higher cytoplasmic bax positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [44.4% (12/27) vs 11.7% (2/17), respectively; P ≤0.05]. CONCLUSION: Existence of apoptotic cells on the basis of TUNEL positivity is shown in intestinal metaplasias co-localizing to both diffuse and intestinal type gastric cancers in this study. Our results also suggested bax expression dependent induction of apoptosis especially in intestinal metaplasia areas adjacent to tumors. These findings strongly support the involvement of apoptotic mechanisms in the process of gastric carcinogenesis especially in the transition from intestinal metaplasia to gastric cancer. It may be suggested that induction of apoptosis in intestinal metaplasia areas adjacent to tumors may involve different mechanisms than induction by chronic inflammation.     

Telomere shortening in gastric carcinoma with aging despite telomerase activation

In the present study, we analyzed both telomere length and telomerase activity in surgical and autopsy samples of non-neoplastic mucosa and carcinomas of the stomach. Telomere length, determined by Southern blot analysis, demonstrated progressive shortening with age in non-neoplastic gastric mucosal specimens from 38 human subjects aged between 0 and 99 years, with an average annual loss rate of 46 base pairs (bp). The mean (±SD) telomere length in 21 gastric carcinomas was 7.0 ± 1.6 × 10³ base pairs (1.6 kbp). In 20 (95%) of the 21 subjects, the values were smaller than those in the non-neoplastic gastric mucosa (mean shortening 1.8 kbp), although a strong correlation was observed for the paired data (r = 0.69, P = 0.0004). Similarly, telomere lengths in carcinomas were shorter than those for intestinal metaplasia (a mean difference of 1.1 kbp). Telomerase activity, estimated using the telomeric repeat amplification protocol assay, was positive in 18 (86%) of the 21 gastric carcinomas, without significant differences among the three histological types (well, moderately, and poorly differentiated adenocarcinomas) or with sex or age. The results suggest that telomere length and possibly shortening rates vary with the individual, and that examination of both non-neoplastic mucosa and tumors is necessary to improve our understanding of the significance of telomerase in neoplasia. Received: 15 December 1999 / Accepted: 9 February 2000     

Comparison of He/icobacter py/ori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients

AIM: To compare Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients in different age groups and from different biopsy sites. METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of gastric ulcer and chronic gastritis patients. Giemsa staining, improved Toluidine-blue staining and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylineosin staining was used for the histological diagnosis of activity of H pylori infection, mucosal inflammation, glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System. RESULTS: Total rate of H pylori infection, mucosal inflammation, activity of H pylori infection, glandular atrophy and intestinal metaplasia in 3 839 gastric ulcer patients (78.5%, 97.4%, 82.1%, 61.1% and 64.2%, respectively) were significantly higher than those in 4 102 chronic gastritis patients (55.0%, 90.3%, 56.2%, 36.8%, and 37.0%, respectively, P<0.05). The rate of H pylori colonization of chronic gastritis in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 33.3%, 41.7%, 53.6%, 57.3%, 50.7%, 43.5%, respectively; in corpus, it was 32.6%, 41.9%, 53.8%, 60.2%, 58.0%, 54.8%, respectively; in angulus, it was 32.4%, 42.1%, 51.6%, 54.5%, 49.7%, 43.5%, respectively. The rate of H pylori colonization of gastric ulcer in <30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and >70 years age groups in antrum was 60.5%, 79.9%, 80.9%, 66.8%, 59.6%, 45.6%, respectively; in corpus, it was 59.7%, 79.6%, 83.6%, 80.1%, 70.6%, 59.1%, respectively; in angulus, it was 61.3%, 77.8%, 75.3%, 68.8%, 59.7%, 45.8%, respectively. The rate of H pylori colonization at antrum was similar to corpus and angulus in patients, below 50 years, with chronic gastritis and in patients, below 40 years, with gastric ulcer. In the other age- groups, the rate of H pylori colonization was highest in corpus, lower in antrum and lowest in angulus (all P<0.05). The rates of glandular atrophy and intestinal metaplasia were higher and earlier in H pylori-positive patients than those without H pylori infection (both P<0.01). In comparison of gastric ulcer patients with chronic gastritis patients, the rate of glandular atrophy and intestinal metaplasia was higher in H pylori-positive patients with gastric ulcer than in H pylori-positive patients with chronic gastritis (both P<0.01); the rate of glandular atrophy and intestinal metaplasia were also higher in H pylori-negative patients with gastric ulcer than in H pylori-negative patients with chronic gastritis (both P<0.01). Both glandular atrophy and intestinal metaplasia were much more commonly identified in the angulus than in the antrum, lowest in corpus (all P<0.01). CONCLUSION: Rate of H pylori infection, glandular atrophy and intestinal metaplasia in gastric ulcer were higher than in chronic gastritis in all-different age -groups. Distribution of H pylori colonization is pangastric in the younger patients. It is highest in corpus, lower in antrum and lowest in angulus in the older age groups. Progression of glandular atrophy and intestinal metaplasia seem to have a key role in the distribution of H pylori colonization. H pylori appears to be the most important risk factor for the development of glandular atrophy and intestinal metaplasia, but it is not the only risk.     

Helicobacter pylori eradication to prevent gastric cancer： underlying molecular and cellular mechanisms

Numerous cellular and molecular events have been described in development of gastric cancer. In this article, we overviewed roles of Helicobacter pylori (H pylori) infection on some of the important events in gastric car-cinogenesis and discussed whether these cellular and molecular events are reversible after cure of the infection. There are several bacterial components affecting gastric epithelial kinetics and promotion of gastric carci-nogenesis. The bacterium also increases risks of genetic instability and mutations due to NO and other reactive oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may alter the frequency of phe-notype change of gastric glands to those with intestinal metaplasia. Host factors such as increased expression of growth factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H py/ori-positive subjects. It is noteworthy that most of the above phenomena are reversed after the cure of the infection. However, some of them including overexpression of COX-2 continue to exist and may increase risks for carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori eradication. Thus, H pylori eradication may not completely abolish the risk for gastric carcinogenesis. Efficiency of the cure of the infection in suppressing gastric cancer depends on the timing and the target population, and warrant further investigation.     

Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue相似文献