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。     

温度对HID染色结果的影响探讨

近年来,许多研究提示分泌硫酸化粘液的胃粘膜大肠化生与肠型胃癌关系密切。高铁二胺—爱先蓝(HID/AB)法能将硫酸化粘液显示成清晰的棕黑色,由于此法稳定、简便、使之成为胃粘膜的常规粘液组化染色。本实验在不同温度和时间的条件下观察HID粘液染色的效果以及背景染色,旨在探讨温度与HID染色结果的相互关系。     

胃癌CEA免疫组化与生物学行为及预后的关系

用PAP法对104例胃癌手术标本进行CEA反应及预后关系的研究。结果显示:胃癌组织CEA分布及含量明显异常。随癌浸润深度增加,CEA阳性率增高,脉管浸润组和淋巴结转移组CEA阳性率明显高于无脉管浸润组及无淋巴结转移组。CEA(-)组5年生存比例明显高于CEA(+)组;在浸润或转移组中,也是CEA(-)组生存比例较CEA(+)组高。提示:CEA(+)肿瘤生物学行为较恶,有扩散和转移的倾向,组织中CEA检测对确定肿瘤浸润,转移及预后有一定价值。     

胃癌及癌旁组织中CDX2和claudin-3的表达及其意义

目的探讨CDX2和claudin-3在胃癌及癌旁组织中的表达及其与临床病理因素之间的关系。方法采用免疫组化SP法检测CDX2和claudin-3在67例胃癌及32例癌旁组织中的表达。结果 (1)CDX2在癌旁正常组织中不表达,癌旁肠化上皮的阳性率(87.5%)明显高于胃癌组织(44.8%,P<0.001)。CDX2在Lauren分型肠型胃癌中的阳性率(62.9%)明显高于弥漫型胃癌(25.0%,P<0.05);CDX2表达与胃癌分化程度呈正相关(P<0.05),而与淋巴结转移和TNM分期呈负相关(P<0.05)。claudin-3在胃癌组织中的阳性率(77.6%)明显高于癌旁正常组织(36.7%,P<0.001),胃癌中claudin-3仅与淋巴结转移呈正相关(P<0.05)。(2)5年生存分析显示:CDX2阳性组胃癌5年生存率(76.7%)明显高于阴性组(43.2%,P=0.01)。claudin-3与胃癌患者5年生存率无明显相关性(P>0.05)。根据CDX2和claudin-3在胃癌中联合表达结果进行生存分析,结果显示CDX2+/claudin-3-的胃癌患者,5年生存率最高(P=0.004)。多因素回...     

胃癌癌胚抗原的分布型式与组织类型及组织发生分型的关系

本文应用免疫组化技术对104例胃癌组织CEA分布进行了观察。发现胃癌组织CEA有三种分布型式:即Ⅰ型(浆型),Ⅱ型(膜型)和Ⅲ型(弱反应型)。粘液癌以Ⅰ型分布为主,分化性癌以Ⅱ型分布为主,差分化癌三种分布型式均有。按组织发生分型,肠型胃癌主要显示Ⅱ型分布,胃型和干细胞型胃癌主要显示夏型分布。提示癌组织CEA分布型式可能与肿瘤分化程度有关,而癌组织CEA含量可能与组织发生有一定关系。     

胃癌中IGFBP-4蛋白的表达及临床意义

目的 探讨IGFBP-4(insulin-like growth-factor-binding proteins-4)蛋白在胃癌发生、发展中的作用.方法 采用免疫组化SP法分别检测正常胃黏膜、胃上皮内瘤变和胃癌组织中IGFBP-4蛋白的表达.结果 20例正常胃黏膜组织中IGFBP-4蛋白阳性率为10%,胃上皮内瘤变组织中的阳性率为36.84%,胃癌组织中的阳性率为81.25%;胃癌组织中IGFBP-4蛋白表达高于胃上皮内瘤变及正常胃黏膜组织(P<0.001),胃上皮内瘤变与正常胃黏膜的差异有显著性(P<0.05);高分化胃癌中IGFBP-4蛋白阳性率为57.14%,低分化胃癌中的阳性率为88.4%,两者之间差异有显著性(P<0.05);早期胃癌阳性率为55.0%,明显低于进展期胃癌86.96%;伴淋巴结转移组阳性率为89.04%,无淋巴结转移组阳性率为66.67%,差异有显著性;而与性别、年龄、肿瘤直径无关.结论 IGFBP-4蛋白的高表达与胃癌的发生、淋巴结转移及临床分期相关.     

糜烂性食管炎、Barrett食管及食管腺癌中SOX2、CDX2的表达及其临床意义

目的探讨CDX2、SOX2在糜烂性食管炎、Barrett食管的3种不同组织类型(胃底型、贲门型、肠化生型)及食管腺癌(esophageal adenocarcinoma,EAC)中的表达及意义。方法采用免疫组化Eli Vision两步法检测CDX2和SOX2在35例贲门组、23例胃底组、14例肠化组、10例糜烂性食管炎组、7例EAC组、10例正常食管下段黏膜中的表达情况。结果 CDX2在肠化组及EAC组中的阳性率均为85.7%,显著高于其他四组(P0.05);CDX2阳性率在贲门组(11.4%)、胃底组(0)、糜烂性食管炎组(0)及正常食管组(0)中的差异无显著性(P0.05)。CDX2在贲门组(75%)及EAC组(66.7%)以(+)为主,差异无统计学意义(P0.05),与肠化组(91.7%)以()为主显著不同(P0.05)。SOX2在Barrett食管三组中的阳性率均为100%,显著高于EAC组(28.6%)(P0.05)。SOX2以(++)表达方式在胃底组(95.7%)及贲门组(74.3%)中差异无统计学意义(P0.05);显著高于肠化组(50%)和EAC组(50%)(P0.05)。SOX2和CDX2的表达在肠化型Barrett食管中呈负相关(P0.05),在贲门组、胃底组、EAC组中无明显相关(P0.05)。结论短段贲门型Barrett食管中CDX2的阳性率不高,可能只是一种柱状上皮化生,与EAC的关系不大;CDX2在鳞状上皮向特殊肠上皮化生转化过程中发挥重要作用,SOX2的沉默促进EAC发生。     

胃粘膜肠化范围及类型在胃癌发生中的作用

胃粘膜肠上皮化生是指胃粘膜出现肠型上皮的现象(简称肠化)。肠化与胃癌的关系已有不少研究,但所得结论仍不完全一致。多数认为肠化与肠型胃癌有直接关系,主张肠型胃癌由肠化上皮癌变而来,肠化属癌前病变。少数则认为肠化是一种伴发现象,不属癌前病变。近年来,随着粘液组化研究的深入开展,有的作者将胃粘膜肠化分为两型:小肠型和结肠型。并认为结肠型肠化与肠型胃癌关系密切,属癌前病变,而小肠型肠化则是胃粘膜损伤的非特异反应。本文目的在于通过40岁以上胃良、恶性病例胃粘膜     

高铁二胺,爱先蓝和PAS的复合粘液组化染色法

高铁二胺、爱先蓝和ＰＡＳ的复合粘液组化染色法苏宝山，李秀林，王康敏，赵世平为了在同一张组织切片，甚至同一个腺体中同时显示硫酸化酸性粘液、非硫酸化酸性粘液和中性粘液３种粘液成分，我们选择了经典的高铁二胺、爱先蓝和ＰＡＳ的复合染色法，旨在观察其对肠化胃粘...     

胃粘液细胞癌的形态特征与组织发生

40例胃粘液细胞癌,来自20例早癌切除和20例活检标本。对粘液细胞癌的形态特征进行了重点观察和描述。粘液组化显示大多数肿瘤(67.5%)分泌混合性中性和酸性粘液,分泌硫酸粘液者占62.5%,但量较少。从粘液细胞癌之形态和组化性质可推测肿瘤之分化时期,进一步证实了粘液细胞癌起源自腺颈部干细胞。     

Detection of sulfated glycoproteins in intestinal metaplasia: a comparison of traditional mucin staining with immunohistochemistry for the sulfo-Lewis(a) carbohydrate epitope

BACKGROUND: Premalignant Barrett's oesophagus (BO) and gastric intestinal metaplasia (IM) show phenotypic variability. Incompletely differentiated sulfomucin rich gastric IM (type III) may have increased malignant potential. The types of sulfated oligosaccharide structures present in IM, BO, and colon have not been fully characterised. AIMS: To compare sulfo-Lewis(a) epitope tissue distribution with high iron diamine (HID) positive sulfomucin in metaplastic, dysplastic, and neoplastic tissues from oesophagus and stomach. METHODS: Sections containing gastric IM or BO (some associated with dysplasia or adenocarcinoma) were stained by the HID/alcian blue (AB) method and immunohistochemically (antibody 91.9H) to detect sulfo-Lewis(a). Based on HID/AB staining, IM was subtyped into type I (complete) or types II and III (incomplete). RESULTS: In total, 125 sections from 38 subjects were studied. Normal squamous oesophagus, normal gastric epithelium, and type I IM were negative for sulfomucin and sulfo-Lewis(a). In type II IM, occasional goblet cells were HID and sulfo-Lewis(a) positive, but sialomucin secreting (AB positive) columnar cells were sulfo-Lewis(a) negative. Type III IM was always sulfo-Lewis(a) positive. Sulfomucin staining in dysplasia and cancer was variable, but HID positive areas were always sulfo-Lewis(a) positive. CONCLUSIONS: Sulfo-Le(a), which is expressed on colonic mucin, is invariably present on sulfomucins in gastric IM and BO. Its presence in incomplete variants of IM and its absence from type I IM emphasises the phenotypic differences between complete and incomplete forms of metaplasia. 91.9H immunostaining is useful in IM subtyping. Characterising the molecular basis of sulfo-Lewis(a) expression may help understand the process of aberrant differentiation.     

胃癌及其胃粘膜病变的粘液组织化学和免疫组织化学的研究

对114例不同组织类型的胃癌及其胃粘膜组织，进行了粘液组织化学和癌胚抗原免疫组织化学研究。结果表明：肠上皮化生（肠化）检出率在萎缩性胃炎对照组高于癌组，癌组的肠化检了率非癌组织高于癌旁组织。肠化细胞是成熟性增生，它和不典型增生及癌均未发现有过渡形式。不典型增生偶见细胞癌变，有时也不易和高分化腺癌鉴别。认为肠化是对有害因子刺激的适应性变化，而不典型增生多系癌前病变。癌胚抗原在不同类型的胃癌组织中分布和量的不同除标志着分泌和释放不同外，可能也有助于判断癌的预后。     

50例胆囊癌黏液组化与免疫组化观察

目的：探讨黏液分泌变化和肿瘤相关抗原表达对胆囊癌早期诊断及其预后判断的价值。方法：采用黏液组化和免疫组化染色对40例胆囊癌,10例胆囊腺瘤,10例慢性胆囊炎的黏液分泌和CEA,CA50,E－cad及PCNA表达进行检测。结果：胆囊癌与胆囊炎和腺瘤相比,分泌硫酸黏液明显减少,唾酸黏液显著增多（P＜0．05）。胆囊癌CEA,CA50阳性表达率显著高于腺瘤和胆囊炎组（P＜0．05）,而E－cad阳性表达率明显降低,伴有转移者E－cad表达更低,胆囊癌PCNA LI高于胆囊炎和腺瘤组（P＜0．01）,CEA,PCNA过度表达者其3年生存率显著降低（P＜0．01）,E－cad过度表达者其3年生存率较阴性组明显增高（P＜0．05）。结论：黏液组化染色和CEA,CA50以及PCNA检测可能有助于胆囊腺瘤恶变和胆囊癌的早期诊断,且CEA PCNA和E－cad检测可作为胆囊癌预后判断的参考指标。     

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).     

Intestinal metaplasia in benign and malignant gastric lesions

The purpose of this study has been to determine the prevalence of intestinal metaplasia (IM) and its subtypes in normal, benign and malignant states, with special reference to the significance of presence as well as location of sulphomucins in the metaplastic epithelium. Sixty-seven specimens of the normal, benign chronic gastric disease and gastric carcinoma have been studied. The overall prevalence of IM in gastric carcinoma has been found to be much higher (67 percent) than in the normal (nil) and benign lesions of stomach (11 percent). The sulphomucins producing IM also has a higher prevalence in gastric carcinoma (70 percent) but can occur in benign conditions also (40 percent). On the other hand Type III IM, characterized by sulphomucins in the columnar cells is seen only in gastric carcinoma, and not in the benign lesions.     

Mucosubstance histochemistry of the normal mucosa and epithelial neoplasms of the large intestine

Histochemical properties of mucosubstances in normal mucosa and neoplasms of 100 operated cases with colonic carcinoma were investigated by using several new methods, such as paradoxical concanavalin A (con A) staining and modified PAS reactions for sialic acids. Acidity of goblet cell-type mucin (GCM) of the normal mucosa varied with the depth of the crypt, as well as with different segments of the large intestine, whereas surface coat-type mucin (SCM) mainly consisted of sulfomucin throughout the large intestine. In addition, the PAS reactivity revealing the presence of O-acetylated sialic acid and the labile class III con A reactivity were demonstrated as hallmarks characterizing the colonic GCM. In carcinoma tissues, sialomucin was more abundant than in the normal mucosa. Goblet-type tumor cells were found in 59 cases. Moreover, O-acetylated sialic acid and the labile class III con A reactivity persisted in GCM of the goblet-type tumor cells. GCM of the adjacent mucosa of the neoplasms showed a decrease in sulfomucin in 95 cases and a marked increase in the labile class III con A reactivity in 97 cases, while the histochemical properties of SCM in this region remained unchanged.     

Histological risk markers for non-cardia early gastric cancer

There are limited data regarding the prognostic value of the pattern of mucin expression in IM. To examine the role of the type of IM and pattern of mucin expression in IM as histological risk markers of gastric cancer, 80 patients with a history of endoscopic mucosal resection (EMR) for early gastric cancer and 80 sex and age-matched controls were studied. Serum levels of pepsinogen (PG) were measured by RIA, and MUC2, MUC5AC and MUC6 were evaluated immunohistochemically. There is a significant association between types of IM and atrophic scores or PG levels. The most incomplete IM (type II and III) preserving gastric mucin is the gastric and intestinal mixed (GI) type, whereas the complete type is the intestinal (I) type especially in the corpus lesser curve. Gastric cancer was most significantly associated with incomplete IM in the corpus lesser curve (OR=6.4; 95% CI, 2.0–21, p=0.002). Asynchronous multiple lesions were associated with incomplete IM in the corpus greater curve (OR=4.8; 95% CI, 1.4–16, p=0.01). Classification of IM obtained using fixed-point biopsy samples may enhance the ability of surveillance programs to detect patients at increased risk of gastric cancer.     

Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach

AIMS: To study multiple gene expression patterns and their roles in the process of gastric carcinogenesis. METHODS AND RESULTS: Using a high-throughput tissue microarray technique, 169 specimens from gastric carcinomas, precursor lesions and normal mucosa were immunostained on a series of tissue chips for p53, p21(WAF1/CIP1) cyclin E, Bcl-2, c-met and mucin 5AC expression. The overexpression of p53 was observed in 10.7% of low-grade dysplasia (LGD), 38.1% of high-grade dysplasia (HGD) and 39.6% of intestinal type gastric carcinoma (IGC). Expression of p21(WAF1/CIP1) was found in 47.6% of incomplete intestinal metaplasia (IM), 36.7% of dysplasia (Dys) and 29.5% of IGC. The overexpression of cyclin E was more frequently present in carcinomas than in Dys (P < 0.05); moreover, high-level expression (> 25% in extent) of cyclin E was observed only among IGC. Abnormal Bcl-2 expression was present in 81.0% of incomplete IM, 69.4% of Dys and 22.9% of IGC. Along with progression of the lesion, the expression of c-met increased; in contrast, mucin 5AC decreased gradually. CONCLUSIONS: The specific expression pattern in incomplete IM was mucin 5AC+/Bcl-2+/p53-/cyclin E-, while mucin 5AC-/cyclin E+ was specific for IGC. p53 was useful for distinguishing LGD from HGD. High-level expression of cyclin E might be an indicator for malignant transformation of dysplasia.