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。     

胃黏膜癌变过程中环氧合酶-2和C-met蛋白的表达及其意义

目的: 探讨环氧合酶-2 (COX-2)和C-met蛋白在胃黏膜癌变过程中的变化规律及其意义.方法:采用Envision法,用20例慢性浅表性胃炎作为对照组,对38例慢性萎缩性胃炎伴肠上皮化生、38例肠化伴异型增生和76例胃腺癌标本,分别检测COX-2和C-met蛋白的表达情况,并分析其间的相关性.结果: C-met蛋白在慢性浅表性胃炎组的表达低于其他胃黏膜病变组织;从非萎缩性胃炎胃黏膜组织→肠化生→异型增生→胃癌,COX-2的表达逐渐增高.COX-2与C-met蛋白的表达呈正相关.结论: 细胞增殖和凋亡相关因子C-met蛋白与COX-2表达异常在胃黏膜癌变过程中发挥重要作用.     

胃癌相关下调基因在胃癌及癌前病变中的表达及其意义

目的观察胃癌相关下调基因(GDDR)在胃癌及癌前病变中的表达变化,探讨GDDR在胃黏膜癌变过程中的作用和意义。方法应用免疫组化SP法测定经胃镜活检和病理确诊的40例正常胃黏膜组织,40例慢性浅表性胃炎,40例慢性萎缩性胃炎,40例胃的肠上皮化生,20例轻度异型增生,20例重度异型增生和40例胃癌中的GDDR蛋白表达情况。结果从正常胃黏膜组织、慢性浅表性胃炎、慢性萎缩性胃炎、胃肠上皮化生、轻度异型增生、重度异型增生、胃癌的发展过程中,GDDR蛋白表达逐渐下调(平均秩次分别为190.70、182.70、146.24、104.40、70.33、47.20和40.20),差异有统计学意义(P0.05)。结论 GDDR表达下调发生在胃癌形成早期,提示GDDR在胃癌的早期诊断和治疗中起重要作用,有望成为胃癌早诊的分子标记物和分子治疗的新靶点。     

胃部疾病患者组织和血清中白细胞介素23和胃蛋白酶原1的变化及临床意义

目的探讨胃部疾病患者组织和血清中白细胞介素23(IL-23)、胃蛋白酶原1(PG1)的变化及临床意义。方法分别收集慢性浅表性胃炎、慢性萎缩性胃炎伴肠化生以及胃癌患者病变组织及外周血,免疫组织化学染色检测IL-23在这3种胃部疾病组织中的表达,时间分辨免疫荧光分析法定量检测血清PG1的水平,ELISA检测血清IL-23的水平,Pearson相关分析验证慢性萎缩性胃炎伴肠化生及胃癌患者血清中IL-23与PG1的相关性。结果在组织样本中,与慢性浅表性胃炎组相比,慢性萎缩性胃炎伴肠化生组和胃癌组IL-23表达明显增高。与慢性浅表性胃炎组相比,慢性萎缩性胃炎伴肠化生组和胃癌组血清IL-23浓度也明显升高,且呈递增趋势;而PG1浓度则在慢性萎缩性胃炎伴肠化生组和胃癌组中明显降低。Pearson相关性分析显示慢性萎缩性胃炎伴肠化生组和胃癌组中血清IL-23的水平与PG1呈负相关。结论慢性萎缩性胃炎伴肠化生和胃癌患者组织中IL-23高表达,且血清IL-23的水平与PG1呈负相关。     

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。     

胃癌组织cyclinE和p21~(WAF1/CIP1)蛋白表达的意义

目的 :探讨cyclinE和p2 1WAF1/CIP1蛋白在胃癌发生发展中的作用及其表达的意义。方法 :采用免疫组化S P法检测正常胃黏膜、萎缩性胃炎伴肠上皮化生、萎缩性胃炎伴不典型增生各 2 0例和 78例胃腺癌组织中cyclinE和 p2 1WAF1/CIP1蛋白表达。结果 :cyclinE蛋白阳性表达在胃癌组高于正常胃黏膜、萎缩性胃炎伴肠上皮化生组 ,而 p2 1WAF1/CIP1蛋白表达则相反 ,差异均有显著性 (P <0 0 5 ) ;cyclinE、p2 1WAF1/CIP1蛋白表达与胃癌细胞分化程度相关 (P <0 0 5 ) ;有肝转移的胃癌组cyclinE阳性表达率高于无肝转移组 (P <0 0 5 ) ;有淋巴结转移组 p2 1WAF1/CIP1蛋白表达率低于无淋巴结转移组 (P <0 0 5 )。结论 :cyclinE蛋白高表达与 p2 1WAF1/CIP1蛋白失表达可能参与胃癌的发生发展过程 ,检测cyclinE和p2 1WAF1/CIP1蛋白作为反映胃癌病理学特点的参考指标可能有一定意义     

胃癌组织cyclinE和p21^WAF1／CIP1蛋白表达的意义

目的探讨cyclinE和p21WAF1/CIP1蛋白在胃癌发生发展中的作用及其表达的意义.方法采用免疫组化S-P法检测正常胃黏膜、萎缩性胃炎伴肠上皮化生、萎缩性胃炎伴不典型增生各20例和78例胃腺癌组织中cyclinE和p21WAF1/CIP1蛋白表达.结果cyclinE蛋白阳性表达在胃癌组高于正常胃黏膜、萎缩性胃炎伴肠上皮化生组,而p21WAF1/CIP1蛋白表达则相反,差异均有显著性(P<0.05);cyclinE、p21WAF1/CIP1蛋白表达与胃癌细胞分化程度相关(P<0.05);有肝转移的胃癌组cyclinE阳性表达率高于无肝转移组(P<0.05);有淋巴结转移组p21WAF1/CIP1蛋白表达率低于无淋巴结转移组(P<0.05).结论cyclinE蛋白高表达与p21WAF1/CIP1蛋白失表达可能参与胃癌的发生发展过程,检测cyclinE和p21WAF1/CIP1蛋白作为反映胃癌病理学特点的参考指标可能有一定意义.     

胃癌及癌旁黏膜组织中CK7、CK20和Ki-67表达的临床意义

目的 研究CK7、CK20和Ki-67在胃腺癌组织中表达状况及临床意义.方法 采用免疫组化EnVision法检测60例胃癌及癌旁黏膜组织CK7、CK20和Ki-67的表达情况,比较不同组织类型胃腺癌患者CK7、CK20和Ki-67的表达及其相关性.结果 胃癌组织中CK7、CK20和Ki-67的阳性表达率分别为88.33%(53/60)、73.33%(44/60)和96.67%(58/60),癌旁黏膜异型增生中CK7、CK20和Ki-67的表达分别为92.31%(24/26)、84.62%(22/26)和96.15%(25/26),肠上皮化生组织中CK7、CK20和Ki67的表达分别为85.71%(12/14)、78.57%(11/14)和92.86%(13/14),均明显高于癌旁正常黏膜组织(P均<0.05),且阳性强度多为高表达.低分化胃腺癌中CK7、CK20和Ki-67的表达明显强于高分化腺癌,差异具有统计学意义(P＜0.05).CK7、CK20和Ki-67在胃腺癌组织中的表达呈正相关(P＜0.001).结论 CK7、CK20和Ki-67的表达与胃癌分化程度关系密切,可作为预测胃癌评估预后的指标.     

残胃癌与残胃再发癌18例病理分析

总结了着重观察的4例残胃癌和14例残胃再发癌的病理组织学特点:癌变发生在吻合口部者占38.9%;再发癌病例的大体类型、组织学类型、生长方式等两次手术后所见多相同或近似;两组病例的癌旁粘膜除多见萎缩性或萎缩增生性胃炎,中、重度异型增生或肠上皮化生,甚至有的移行到癌之外,可见吻合口附近粘膜呈息肉状增生,粘膜深层腺管囊状扩张或粘膜下异位腺体。文章对残胃癌与再发癌的概念、病因及早期发现进行了初步分析。     

Gankyrin在胃癌及癌前病变中的表达及意义

目的 探讨Gankyrin在胃癌及癌前病变(包括慢性萎缩性胃炎和胃黏膜上皮的异型增生)中的表达及其意义。方法 采用免疫组织化学法检测Gankyrin在30例正常胃黏膜、60例慢性萎缩性胃炎、30例胃黏膜上皮异型增生和84例胃癌中的表达,同时分析Gankyrin表达和胃癌临床病理学特征的关系。结果 Gankyrin在正常胃黏膜、慢性萎缩性胃炎、胃黏膜异型增生和胃癌组织中均有不同程度的表达,而且表达差异具有统计学意义(P0.05)。Gankyrin在胃癌中的表达与临床分期和转移相关,和患者的年龄、性别以及肿瘤的大小、组织学分级没有相关性。结论 Gankyrin不仅参与胃癌的早期发生,而且也参与胃癌的发展,Gankyrin有望成为胃癌诊断和防治的靶标。     

IN SITU ANALYSIS OF TISSUE DYNAMICS AND p53 EXPRESSION IN HUMAN GASTRIC MUCOSA

In situ tissue dynamics were studied in 12 cases of human gastric mucosa, including normal gastric body mucosa and gastric glands with intestinal metaplasia, obtained from gastrectomy specimens of adenocarcinoma. Cell proliferation was determined by Ki67 immunoreactivity. DNA fragmentation was studied in situ by TdT-mediated dUTP-biotin nick end labelling (TUNEL). In addition, p53 expression was examined by both immunohistochemistry and mRNA in situ hybridization. In the oxyntic gastric glands, Ki67 immunoreactivity was observed exclusively in the proliferative zone and TUNEL-positive cells were present predominantly in the surface foveolar epithelium. In the gastric glands with complete intestinal metaplasia, Ki67-positive cells were present in the lower portion of the glands and TUNEL-positive cells in the superficial epithelium. In the gastric glands with incomplete intestinal metaplasia, TUNEL-positive cells were detected in the lower gastric glands adjacent to cells immunoreactive for Ki67; the proportion of these gastric glands with TUNEL-positive cells (40 out of 108 glands) was significantly higher than for oxyntic glands (94 out of 620 glands) or for glands with complete metaplasia (31 out of 254 glands). Relatively strong p53 immunoreactivity and mRNA hybridization were also observed in the proliferative and apoptotic areas of gastric glands with incomplete intestinal metaplasia. These results indicate that incomplete intestinal metaplasia is associated with increased cell turnover and p53 overexpression, possibly in response to various noxious or DNA-damaging stimuli.     

Evaluation of apoptosis along with BCL-2 and Ki-67 expression in patients with intestinal metaplasia

The primary aim is to compare individuals with intestinal metaplasia (IM), chronic active gastritis (CAG), and normal gastric mucosa (NGM) in terms of apoptosis, proliferation, and Bcl-2 expression. The secondary aim is to determine whether these parameters are different between patients with and without gastric cancer in first-degree relatives. We enrolled 106 patients whose histopathological results were consistent with IM (n: 42), CAG (n: 51), or NGM (n: 13). Antral biopsies were immunohistochemically stained for Bcl-2 and Ki-67 expression. Apoptosis was detected using TUNEL assay. While no significant difference was determined between three groups with regard to apoptosis and Bcl-2 expression (p>0.05), Ki-67 expression was significantly higher in the IM group when compared with the CAG and NGM groups (29.90±22.87 vs. 18.18±16.22 vs. 18.54±20, respectively; p=0.012). Helicobacter pylori was determined to increase apoptosis (49.3% vs. 25.7%, p<0.05), nevertheless, it had no significant effect on proliferation and Bcl-2 expression. Bcl-2 and Ki-67 expression and apoptosis were not different among patients with and without a history of gastric cancer in first degree relatives. Although intestinal metaplasia cases demonstrate an increase in proliferation, no elevation is observed in apoptosis. This can be an important factor in the progression to gastric cancer.     

Gastric cancer: problems in histogenesi

Intestinal metaplasia in the mucosa adjacent to a gastric carcinoma suggests that some carcinomas of the stomach might arise from metaplastic mucosa, as well as the existence of a gastric cancer with morphological features resembling intestinal mucosa. In this study, the extent of intestinal metaplasia of adjacent mucosa, the type of intestinal metaplasia (complete or incomplete), the degree of tumour differentiation, the type and quantity of mucins secreted by neoplastic cells and morphological features of the tumours were evaluated in 59 cases of gastric carcinoma. An analysis of the findings suggests that a carcinoma may arise in the stomach with features of association with incomplete metaplasia and histochemical and histological patterns which mimic carcinomas of the large intestine.     

Cell damage and proliferation in human gastric mucosa infected by Helicobacter pylori--a comparison before and after H pylori eradication in non-atrophic gastritis

Helicobacter pylori (HP) is believed to be involved in the transition from normal gastric mucosa to atrophic gastritis and intestinal metaplasia. Infection with the organism is one of the risk factors for development of intestinal-type gastric adenocarcinoma, possibly through altered cell turnover. Medical eradication of HP is widely performed for the treatment of peptic ulcers and other upper gastrointestinal disorders. Eradication of HP may affect altered cell turnover of the gastric mucosa caused by the infection, but there are few reports comparing sterilized mucosa with HP-infected and non-infected mucosa. In this study, we examined cell damage using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), in situ nick translation (ISNT), and cell proliferation by Ki 67 immunohistochemistry staining in gastric mucosa before and after HP eradication and in non-infected gastric mucosa. We then compared these findings using endoscopic gastric biopsy specimens. Labeling indices of TUNEL (2.46 +/- 1.22), ISNT (1.13 +/- 0.42), and Ki67 (21.8 +/- 6.14) in tissue from which HP had been eradicated were significantly lower than those of HP-infected mucosa (6.36 +/- 2.26, 4.00 +/- 1.62, 45.8 +/- 5.35, for TUNEL, ISNT, and Ki67, respectively). There were no significant differences between formerly infected and non-infected mucosa (TUNEL: 2.26 +/- 0.69, ISNT: 1.29 +/- 0.63, Ki67: 23.5 +/- 8.20). These results indicate that medical HP eradication results in decreased cell proliferation and damage, restoring the condition seen in non-infected mucosa. Thus, HP eradication may be effective, not only in the treatment of gastric ulcers or gastric symptoms, but also in the prevention of gastric carcinoma.     

Gastric and Intestinal Phenotypic Expression of Human Stomach Cancers as Revealed by Pepsinogen lmmunohistochemistry and Mucin Histochemistry

Gastric and intestinal phenotypic expression in 223 surgically obtained primary gastric cancers and their histogenetic relationship to intestinal metaplasia in the surrounding gastric mucosa were studied by mucin histochemistry and pepsinogen (Pg) immunohistochemistry. Histochemical differentiation of mucins (paradoxical concanavalin A, the galactose oxidase-Schiff sequence and sialidase galactose oxidase Schiff) and immunohisto chemical staining of Pgs I and II, allowed differentiation of gastric cancer cells from different histological categories into gastric elements including mucous neck cells, pyloric gland cells and surface mucous cells or intestinal elements including goblet cell and intestinal absorptive cell types. Of 122 papillary and tubular adenocarcinomas, 33 (27.1%) consisted mainly of gastric type cells and 42 (34.4%) predominantly of intestinal type cells. The remainder (38.5%) consisted of mixtures of gastric- and intestinal-type cells. Of 101 poorly differentiated adenocarcinomas, signet ring cell carcinomas and mucinous adenocarcinomas, 59 (58.4%) consisted mainly of gastric-type cells and 20 (19.8%) mainly of intestinal-type cells. Seven out of 35 papillary and tubular adenocarcinomas consisting mainly of gastric type cancer cells were surrounded by mucosa with intestinal metaplasia. Conversely, 10 out of 40 papillary and tubular adenocarcinomas consisting mainly of intestinal-type cancer cells were observed in non metaplastic gastric mucosa. Thus no relationship as regards intestinal phenotypic expression was found between gastric cancers and surrounding gastric mucosa.     

Ciliated Cells in the Human Gastric Mucosa Evidence of Metaplastic Change

In the gastric mucosa of Japanese patients, ciliated cells were found in association with intestinal metaplasia. The cells occurred frequently in the pyloric mucosa of nearly half of the cases examined but rarely in the cardiac mucosa of total 12 cases, but never adjacent to the chief cells of gastric glands. The ciliated cells were always found in the basal part of cardiac and pyloric glands, but never in the surface or in the foveolar epithelium. Furthermore, ciliated cells containing a few small mucus granules and simultaneously possessing numerous cilia and basal bodies were noted. Ciliated cells in the gastric mucosa have been found mainly in elderly Japanese patients, but were also observed exceptionally in one Chinese, two Swedes and one American. These ciliated cells are not present in the normal human gastric and intestinal mucosa, and therefore a new term, "ciliated metaplasia", is proposed for their occurrence. Acta Pathol Jpn 40: 98–106, 1990.     

p53 mutations and microsatellite instabilities in the subtype of intestinal metaplasia of the stomach

To investigate the potential implication of the subtype of intestinal metaplasia in the progression to the gastric carcinoma, we analyzed the mutations of the p53 gene and microsatellite instability (MSI) both in the complete type (type I) and in the sulphomucin-secreting incomplete type (type III) intestinal metaplasia located adjacent to the gastric carcinoma. p53 mutations were observed in 13.3% of type I, in 6.6% of type III intestinal metaplasia, and in 40% of gastric carcinoma. The difference between p53 mutations observed in type I and type III intestinal metaplasia was not statistically significant. No identical mutation of the p53 gene was found in the intestinal metaplasia and carcinoma specimens from the patients. There was no case of intestinal metaplasia showing MSI. In gastric carcinomas, MSI was observed in six cases (40%). The cases harboring BAT-26 instability did not have the mutation of the p53 gene. These data suggest that intestinal metaplasia adjacent to gastric carcinoma, irrespective of its subtype, do not have the genetic alterations as showing in their carcinoma tissues.     

不同年龄组人群胃粘膜病变的观察(3258例胃非恶性肿瘤标本的分析研究)

本文对我国3258例非胃恶性肿瘤标本不同年龄组人群的胃粘膜良性病变进行了观察,发现CSG、CAG、IM、ATP(异型增生)、胃和十二指肠溃疡的检出率均随年龄增长有增高的趋势,高发年龄除CSG为30～39岁外,余者均为40～49岁,此与我国胃癌高发年龄(50～59岁)相比均提前10～20年,符合文献上记载从癌前状态发展为癌前病变直至癌的所需时间。各种病变检出率为IM1914例(58.75%)、CAG1850例(56.78%)、CSG1356例(41.62%)、GU1335例(40.98%)、DU 1221例(37.48%)。ATP1113例(34.16%)。在CAG中IM和ATP均高,在伴ATP中,肠化型CAG(37.35%)又高于非肠化型(5.72%),因此伴异型肠化的萎缩性胃炎可能与我国胃癌高发密切相关。     

Gastric or intestinal phenotypic expression in the carcinomas and background mucosa of multiple early gastric carcinomas

AIMS: The differences in phenotypic expression between multiple early gastric carcinomas (EGCs) and solitary EGCs were evaluated in this study. METHODS AND RESULTS: Fifty-three cases (53 lesions) of solitary EGCs and 50 cases (112 lesions) of multiple EGCs were studied. According to the classification of intestinal metaplasia, the phenotypes of carcinomas and background mucosa were classified into four categories-complete intestinal type, incomplete intestinal type, gastric type and unclassified type-based on the combination of expression of CD10 (small intestinal brush border), MUC2 (intestinal goblet cell), HGM (gastric foveolar epithelium) and Con A (gastric pyloric glands). The incidence of gastric-type carcinomas (48%) and the incidence of incomplete intestinal-type background mucosa (75%) among the multiple EGCs was higher than among the solitary EGCs. There was a significant difference in distribution of phenotypic expression of carcinomas and background mucosa between the solitary EGCs and the multiple EGCs, the latter being associated with incomplete intestinal metaplasia. CONCLUSIONS: Both the carcinomas and the background mucosa of multiple EGCs have an unstable status, since they more commonly possess the hybrid phenotype of the stomach and the small intestine than does solitary EGC. Such instability is considered to contribute to a high neoplastic potential and the multiple occurrence of carcinomas.     

T (Thomsen–Friedenreich) antigen and other simple mucin-type carbohydrate antigens in precursor lesions of gastric carcinoma

In a previous report we suggested that T antigen appeared to be associated with gastric carcinoma. To verify this hypothesis and characterize the pattern of expression of simple-mucin type carbohydrate antigens (Tn. sialyl-Tn and T before and after neuraminidase) in normal gastric mucosa and precursor lesions of gastric carcinoma, we studied the mucosa adjacent to 100 cases of gastric carcinoma, gastric biopsies of 60 dyspeptic patients, eight adenomatous polyps and eight hyperplastic polyps. The expression of the antigens was more related to the cell type and underlying lesions than to the coexistence of carcinoma. The most distinctive findings concerned intestinal metaplasia, dysplasia and hyperplastic lesions. In intestinal metaplasia, Tn was found mostly in columnar cells and sialyl-Tn in goblet cells. T was more prevalent in incomplete intestinal metaplasia than in complete. A high prevalence of sialyl-Tn expression and cell membrane immunoreactivity for T antigen, similar to those previously found in gastric carcinomas, were observed in three adenomatous polyps, one hyperplastic polyp, five cases of adenomatous dysplasia in the neighbourhood of intestinal carcinomas and four cases of marked foveolar hyperplasia, three of which were from the mucosa adjacent to diffuse carcinomas. We conclude that adenomatous and hyperplastic lesions share with gastric carcinomas features of aberrant glycosylation, namely the cell membrane expression of T antigen.