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。     

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。     

血清PG和MG7-Ag联合检测在胃癌诊断中的应用研究

目的探讨血清胃蛋白酶原(PG)及其亚群(PGI、PGI/PGⅡ)和胃癌相关抗原(MG7-Ag)的联合检测对胃癌的诊断价值及预后判断的意义。方法采用增强免疫比浊法检测PG及ELISA法检测MG7-Ag在各受试者血清中的含量。结果胃癌组的血清PGI、PGI/PGⅡ(PGR)含量明显低于各对照组(P<0.01);萎缩性胃炎组血清PGI、PGR含量明显低于健康对照组、胃溃疡组及浅表性胃炎组(P<0.05);胃溃疡组和浅表性胃炎组的血清PGI含量明显高于健康对照组(P<0.05)。胃癌组血清MG7-Ag含量明显高于各对照组(P<0.01);萎缩性胃炎组血清MG7-Ag含量明显高于健康对照组、胃溃疡组及浅表性胃炎组(P<0.05)。联合检测阳性率最高为90%。胃癌患者术后PGI含量很低,MG7-Ag含量也明显降低(P<0.01),但当胃癌复发后PGI及MG7-Ag含量均明显升高(P<0.05)。结论血清MG7-Ag和PG的含量变化有助于胃癌的诊断、判断胃癌的复发及转移。     

联合检测血清抗HpAb、胃泌素-17和MG7-Ag对胃癌诊断的临床意义

目的研究联合检测血清抗HpAb、胃泌素-17和MG7-Ag对胃癌诊断的临床意义。方法选取2007年12月至2017年12月来我院普外科就诊的202例患者作为实验组,选取来我院体检中心接受体检的50例健康志愿者作为对照组,所有受试者进行血清抗HpAb、G-17和MG7-Ag检测及染色内镜检查。结果胃癌组抗HpAb水平显著高于对照组和胃良性疾病组(P <0. 05);胃癌组G-17、MG7-Ag水平显著低于对照组和胃良性疾病组(P <0.05);对照组联合检测的阳性检出率显著低于单项血清抗HpAb、G-17和MG7-Ag检测(P <0.05);胃良性疾病患者联合检测的阳性检出率显著高于单项血清抗HpAb、G-17和MG7-Ag检测(P<0.05);胃癌患者联合检测的阳性检出率显著高于单项血清抗HpAb、G-17和MG7-Ag检测(P<0.05);联合检测的灵敏度、特异性和准确性均高于单项血清抗HpAb、G-17、MG7-Ag检测(P<0.05)。结论联合检测血清抗HpAb、胃泌素-17和MG7-Ag对胃癌进行诊断,能够提高胃癌临床诊断的灵敏度、特异性和准确性,对胃癌的早期发现具有重要的临床诊断意义。     

胃癌中Bmi-1蛋白的表达及意义

目的利用胃癌组织芯片探讨Bmi-1蛋白在胃癌组织中的表达及意义,为胃癌的诊断及预后判定提供新指标。方法采用免疫组化ABC法检测90例胃癌和8例正常胃组织中Bmi-1蛋白的表达。结果 Bmi-1蛋白在胃癌组织中的阳性率为75.6%,而在正常胃组织中的阳性率为0,两组之间差异有显著性(P<0.001)。Bmi-1蛋白的阳性率与病理学分级呈正相关。进展期胃癌组织中Bmi-1蛋白的阳性率明显高于早期胃癌(P<0.01),并与浸润深度呈正相关。有淋巴结转移、脉管侵犯及远处转移的胃癌组织中Bmi-1蛋白的阳性率明显高于无淋巴结转移、脉管侵犯及远处转移者(P<0.01,P<0.05)。结论 Bmi-1蛋白的高表达在胃癌的发展过程中起重要作用,与胃癌的病理学分级、淋巴结转移、血管转移及远处转移密切相关。     

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。     

胃癌中HSDL2过表达与临床病理特征的相关性

目的探讨羟基类固醇脱氢酶样蛋白2(hydroxysteroid dehydrogenase like 2,HSDL2)在胃癌中的表达及与临床病理特征的关系。方法采用免疫组化SP两步法检测HSDL2蛋白在90例胃癌和20例正常胃组织中的表达,分析HSDL2蛋白过表达与胃癌临床病理特征的关系,并采用GEPIA数据库进行生存分析。结果HSDL2蛋白主要定位于胃癌细胞SGC-7901和AGS的细胞质中。UALCAN数据库分析结果显示:胃癌组织中HSDL2 mRNA的表达水平明显高于正常胃组织(P<0.05)。HSDL2蛋白在胃癌组织中过表达,强阳性率为58.9%(53/90),显著高于正常胃组织(5.0%,1/20)(P<0.01)。HSDL2蛋白表达与胃癌分化程度、临床分期及肿瘤直径密切相关(P均<0.05),与患者性别、年龄及淋巴结转移无明显相关性。GEPIA数据库分析结果显示,HSDL2蛋白过表达胃癌患者无瘤生存率低于HSDL2蛋白低表达患者(P<0.05)。结论HSDL2在胃癌组织中明显过表达,其表达水平与胃癌的发生、发展及不良预后密切相关,有望成为胃癌患者预后评估的重要指标。     

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。     

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。     

The prognostic value of sulphomucin positive intestinal metaplasia in the development of gastric cancer

Gastric biopsy specimens from 230 patients with chronic atrophic gastritis were investigated with the use of mucin stains for the presence and type of intestinal metaplasia. Metaplasia was not shown in 59 cases; 92 of the 171 cases with metaplasia were sulphomucin positive and 79 were negative. The patients were followed-up from 1976 to 1985. Eight patients were registered as having gastric cancer over this period. However, five of them had to be eliminated from the study because on careful review of all the clinical data it was clear that they had gastric cancer at the time of the biopsy. Two of the three remaining patients had sulphomucin negative biopsies. Thus, only one patient out of 90 with chronic atrophic gastritis and sulphomucin positive intestinal metaplasia developed gastric cancer when followed-up for 8-9 years. None of the patients with unequivocal type IIb metaplasia developed gastric cancer. We conclude that sulphomucin positive intestinal metaplasia does not identify a high risk group and its recognition is thus of no value in surveillance for gastric cancer.     

Role of intestinal metaplasia in the histogenesis of gastric carcinoma.

Recent evidence suggests that intestinal metaplasia (IM) cannot be regarded as a single entity. A simple classification of IM and its variants based on histological and mucin histochemical criteria was devised, and the incidence of IM subtypes in cancerous and benign gastrectomy specimens was recorded. A particular subtype was associated with 'intestinal' cancers but not with tumours considered to arise in normal gastric epithelium (P < 0.01) or with benign lesions (P < 0.01). This subtype appeared to lack absorptive cells at light microscopic level and secreted both neutral and acid mucins, including marked amounts of sulphomucin but no O-acetyl sialomucin.     

Immunohistochemical detection of O-acetylated sialomucins in intestinal metaplasia and carcinoma of the stomach

Eighty-two selected gastric mucosal biopsy or resection specimens were stained both conventionally, to classify subtypes of intestinal metaplasia and carcinoma, and immunohistochemically with a mouse monoclonal antibody (MMM-17), raised against normal human colonic mucin, which has an affinity for di- and/or tri-O-acetylated sialomucin. The aims of the study were to reassess the prevalence of O-acetylated sialomucins in normal, metaplastic and carcinomatous gastric mucosa and to investigate whether the production of these mucins by intestinal metaplasia is related to its associated mucosal pathology. O-acetylated sialomucins were not seen in normal mucosa. They were, however, prevalent in all sub-types of metaplastic (64.8%) and carcinomatous (42.9%) mucosa. Type 1 intestinal metaplasia was significantly more likely to contain this type of mucin if Helicobacter pylori infection was identifiable in the adjacent gastric mucosa (81.0% v. 38.5%, P < 0.025). Type 3 showed a similar, albeit nonsignificant, relationship (100% v. 62.5%). O-acetylated sialomucins are, therefore, much more prevalent in gastric intestinal metaplasia and carcinoma than previously recognized by conventional staining techniques. The production of this type of mucin by intestinal metaplasia may reflect an adaptive response to alterations in the luminal environment such as an increase in bacterial content.     

The expression of hepatocyte nuclear factor-4alpha, a developmental regulator of visceral endoderm, correlates with the intestinal phenotype of gastric adenocarcinomas

AIMS: Hepatocyte nuclear factor (HNF)-4alpha is a developmental regulator of the visceral endoderm, which is expressed in the embryonic gut and later in the adult intestine and colon. However, adult gastric mucosa does not express HNF-4alpha. We investigated the possible involvement of HNF-4alpha in intestinal metaplasia and the intestinalisation of gastric adenocarcinomas. METHODS: Thirty-five cases of adenocarcinomas and 46 cases of adjacent non-neoplastic mucosa with (22 lesions) or without (24 lesions) intestinal metaplasia were immunostained for HNF-4alpha. The gastric or the intestinal phenotype was also examined using immunohistochemistry for MUC5AC, MUC2, CD10, and gastric-type mucin (GTM). Adenocarcinomas were classified into the gastric type (G-type, 42.9%), the mixed gastric and intestinal type (GI-type, 31.4%), and the intestinal type (I-type, 25.7%). RESULTS: The HNF-4alpha expression was exclusively seen in glandular cells with intestinal metaplasia, which was correlated with MUC2 expression (p<0.05) and inversely correlated with MUC5AC expression (p<0.05). All adenocarcinomas more or less expressed HNF-4alpha, with an intense expression being seen in the I-type (p<0.01) and in well-differentiated adenocarcinomas (p<0.03). CONCLUSIONS: HNF-4alpha expression is associated with the intestinal phenotype of non-neoplastic and neoplastic gastric glandular cells, suggesting a possible involvement in the establishment and/or maintenance of the intestinal phenotype of the gastric mucosa and adenocarcinomas.     

Sulphomucins favour adhesion of Helicobacter pylori to metaplastic gastric mucosa.

AIMS: To assess the influence of sulphomucin secretion on Helicobacter pylori colonisation and adhesion to metaplastic gastric cells. METHODS: Gastric biopsies from 230 H pylori positive patients with intestinal metaplasia were analysed. Sulphated mucins and H pylori were visualised using a new technique combining high iron diamine-alcian blue mucin stains with the Steiner silver stain for the bacteria. RESULTS: Sulphomucin secretion anywhere in the mucosa and a histological diagnosis of dysplasia increase the risk of H pylori adhesion to metaplastic cells (odds ratios 19.9 and 4.3, respectively). However, only 9.4% of cases showing sulphomucin secretion and 10.8% of cases with dysplasia had evidence of adhesion of H pylori bacteria to metaplastic cells. CONCLUSIONS: The findings suggest that H pylori may play a role in the advanced stages of carcinogenesis. It will be of interest to investigate if the relative small proportion of type III metaplasias that actually progress to carcinoma show persistence of H pylori.     

Significance of acid-mucin-positive nongoblet columnar cells in the distal esophagus and gastroesophageal junction

Acidic mucin-positive nongoblet columnar cells (NGCC) have recently been observed in the surface epithelium of the gastroesophageal junction (GEJ) and distal esophagus in resections from patients with traditional long segment (>3 cm) Barrett's esophagus (BE). However, the significance of finding acidic mucin-positive NGCC in the surface epithelium of biopsy specimens from the distal esophagus/GEJ region in the absence of goblet cells (GC) remains unknown. Therefore, to determine the significance of mucin histochemical changes in the distal esophagus/GEJ region, we analyzed and compared the types, prevalence, and distribution of neutral and acidic mucins in biopsy specimens obtained from 2 groups of patients: those with (32 patients) and those without (107 patients) GC identified in this area. Various mucin histochemical stains (PAS-Ab pH 2.5, HID-Ab pH 2.5, PB/KOH/PAS) were used to identify neutral mucins, acidic mucins (sialomucins and sulphomucins), and o-acetylated sialomucins. The results were compared between the 2 patient groups and correlated with the clinical, endoscopic, and pathologic features. Compared with patients without GC, patients with GC had a significantly higher male/female ratio and a higher proportion of patients with greater than 3 cm of columnar epithelium within the esophagus. Acidic mucin (sialomucin and sulphomucin)-positive NGCC in the surface, foveolar, and glandular epithelium did not show any correlation with any of the clinical, endoscopic, or pathologic features, such as esophagitis, carditis, antritis, Helicobacter pylori infection, or length of columnar epithelium in the distal esophagus. However, acidic mucin-positive NGCC correlated strongly with the presence of GC (P < .001). For example, sialomucin-positive NGCC were present in 28 of 32 (88%) patients with GC compared with 31 of 107 (29%) patients without GC (P < .001). Similarly, sulphomucin-positive NGCC were present in 20 of 32 (62%) patients with GC, compared with 11 of 107 (10%) patients without GC (P < .001). Of the non-GC cases, all biopsy specimens that stained positively for sulphomucin in surface NGCC (11 specimens), except one, showed staining restricted to the surface of multilayered epithelium, a distinctive type of epithelium that shows morphological, ultrastructural, and cytochemical features of both squamous and columnar epithelium. Sialomucin positivity in surface NGCC from the distal esophagus/GEJ region is a sensitive (sensitivity 88%), but nonspecific (specificity 71%), indicator of GC metaplasia. In contrast, sulphomucin expression in NGCC from the same anatomic area is a less sensitive (sensitivity 62%), but more specific (specificity = 90%) marker for the presence of metaplastic epithelium, of either the GC or the multilayered epithelial cell type and thus may represent an early or incomplete form of intestinal metaplasia.     

Endocrine cells in intestinal metaplasia of the stomach

In this study we have investigated the mucin profile and the endocrine cell population in gastric endoscopic biopsies from 22 patients affected by chronic gastritis and intestinal metaplasia and in five surgical specimens of stomachs removed because of intestinal-type carcinoma (4) or peptic ulcer (1). High iron diamine-Alcian blue (HID-Ab) staining and peptide immunocytochemistry (peroxidase anti-peroxidase technique) were used. Forty-one foci of intestinal metaplasia were detected, 15 produced sulphomucins and 26 sialomucins. Of the endocrine cells investigated, gastrin and somatostatin cells were the most frequently observed, while cholecystokinin, glucose-dependent insulinotropic peptide-, secretin- and enteroglucagon-containing cells were also found in the metaplastic areas, but less frequently. No significant correlation was found between the type of mucin and the types of endocrine cells present, the latter usually resembling those normally found in the small intestine. On the basis of these results we conclude that intestinal metaplasia involves mucin- and peptide-producing cells of the stomach in a variable manner, with no correlation between the two.