胃粘膜肠上皮化生与胃癌的粘液组织化学研究

应用粘液组化技术对１８５例胃良恶性疾病进行了研究。结果：胃良恶性疾病伴肠化检出率无明显差异;但含有硫酸粘液的结肠型肠化在胃癌癌旁检出率明显高于良性疾病组。不同分化程度胃癌的转移及术后生存率无明显差异;但含有酸性粘液的肠型、混合型胃癌的淋巴结转移率明显较仅含中性粘液的胃型胃癌高。提示：结肠型肠化与胃癌有一定关系;癌细胞产生大量酸性粘液可能有利癌细胞的扩散与转移,对胃癌病人的预后有一定影响     

胃癌癌旁肠化上皮酶组织化学研究

本文应用酶组化方法对６０例胃癌癌旁粘膜中４７例肠化上皮（７８．３％）的破性磷酸酶（ＡＬＰ）、酸性磷酸酶（ＡＣＰ）、胞嘧啶单核苷酸酶（ＣＭＰ）、葡萄糖－６－磷酸酶（Ｇ－６－ｐａｓｅ）、焦磷酸硫胺素酶（ＴＰＰａｓｅ）、５－核苷酸酶（ＳＮａｓｅ）、三磷酸腺苷酶（Ｍｇ２＋－ＡＴＰａｓｅ,Ｃａ２＋－ＡＴＰａｓｅ）和细胞色素氧化酶（ＣＣＯ）等九种细胞器标志酶进行了定位观察。结果发现肠化上皮吸收细胞上述酶活性均较强,且分布具有极性,杯状细胞酶反应较弱,主要位于细胞基底部。癌旁粘膜肠化阳性率为７８．３％,其中ＡＬＰ阳性的酶完全型肠化和ＡＬＰ阴性的酶不完全型肠化分别占５３．２％,４６．８％,两者出现率相近。酶完全型肠化ＡＬＰ阳性率在胃分化型癌及未分化型癌瘤旁分别占６９．２％和３３．３％。ＡＬＰ阳性率在胃分化型及未分化型癌组织内分别为３５．５％和０％。提示肠化上皮具有与肠上皮相似的代谢特征,酶完全型肠化和酶不完全型肠化可能是肠化的二种不同的形式,在致癌环境下,二者都有可能转变成癌,其中酶完全型肠化与分化型癌的关系较为密切。     

鲤鱼粘液细胞类型的研究

以阿新蓝－过磺酸雪夫氏染色方法（ＡＢ－ＰＡＳ）观察了鲤鱼粘液细胞的形态和类型。根据ＡＢ－ＰＡＳ染色结果将鲤鱼粘液细胞分成四型：Ⅰ型为红色,ＡＢ阴性,ＰＡＳ阳性,含中性粘多糖;Ⅱ型为蓝色,ＡＢ阳性,ＰＡＳ阴性,含酸性粘多糖;Ⅲ型为紫红色,ＡＢ与ＰＡＳ均为阳性,同时含有中性粘多糖和酸性粘多糖,但以中性粘多糖为主;Ⅳ型为蓝紫色,ＡＢ与ＰＡＳ均为阳性,同时含中性粘多糖和酸性粘多糖,但以酸性粘多糖为主。     

胃印戒细胞癌的粘液组织化学和免疫组织化学研究

应用粘液组化及免疫组化技术对１５例胃印戒细胞癌进行了研究。结果：癌细胞可分为Ⅰ、Ⅱ、Ⅲ三型,三型细胞常混合存在;癌细胞以分泌酸性粘液为主,部分癌细胞分泌中性粘液,全部含有硫酸粘液;胃印戒细胞癌ＣＥＡ阳性率１００％,ＣＥＡ分布丧失了极性;电镜下癌细胞ＣＥＡ同时分布于细胞膜及胞浆内膜结构中。上述结果进一步支持了癌细胞起源于胃原始干细胞的看法;而癌细胞分泌的大量粘液及ＣＥＡ的异常分布可能易于导致印戒细胞癌的浸润及转移。     

胃粘膜肠上皮化生与胃癌关系的组织化学和免疫组织化学研究

应用ＡＢ（ｐＨ１．０）ＫＯＨ／ＰＡＳ粘液组织化学和ＡＢＣ法凝集素标记,对１９０例胃粘膜病变标本进行观察。结果表明,结肠不完全型肠上皮化生多见于肠型癌（ＩＴＣ）及其癌旁组织。两型肠化在弥漫型癌（ＤＴＣ）中无显著差异。５种凝集素受体的含量和分布的差异与胃癌的组织学类型和分化程度有关。ＷＧＡ、ＲＣＡ和ＰＮＡ主要标记在ＤＴＣ中,与ＩＴＣ相比,有非常显著的差异（Ｐ＜０．０１）。其染色水平随肿瘤分化程度的降低而升高。ＣｏｎＡ和ＤＢＡ主要标记在ＩＴＣ和伴有肠化的慢性萎缩性胃炎中。凝集素肠化分型与粘液肠化分型基本相符。我们认为结肠不完全肠化与ＩＴＣ的发生关系密切,而小肠型和结肠完全型肠化可能与ＤＴＣ的发生有关。     

乙型肝炎病人重叠感染丙型肝炎的评价

应用ＥＬＩＳＡ和ＰＣＲ法检测５０２例乙肝病人血清,４０１例ＨＢｓＡｇ阳性血清中,有１１４例（２８．４％）抗－ＨＣＶ和ＨＣＶＲＮＡ双项阳性,２５例（６．２％）ＨＣＶＲＮＡ单项阳性;２１例（５．２％）抗－ＨＣＶ单项阳性。将ＨＢｓＡｇ乙肝病人分成ＨＢＶＤＮＡ,ＨＢｅＡｇ阳性组和ＨＢＶＤＮＡ,ＨＢｅＡｇ阴性组。前者抗－ＨＣＶ阳性率为１１．６％～２０．５％,ＨＣＶＲＮＡ阳性率为１６．２％～２０．５％。后者抗－ＨＣＶ阳性率为２０．２％～５５．６％,ＨＣＶＲＮＡ阳性率为２３％～６０．３％。结果说明长期携带ＨＢＶ者和慢性乙肝病人均可重叠ＨＣＶ感染。ＨＢＶＤＮＡ阳性组抗－ＨＣＶ和ＨＣＶＲＮＡ阳性率明显高于ＨＢＶＤＮＡ阳性组     

南方鲇消化道杯状细胞分布及类型探讨

本研究应用阿利新蓝－过碘酸雪夫氏（ＡＢ－ＰＡＳ）染色方法对南方鲇（Ｓｉｌｕｒｕｓ　ｍｅｒｉｄｉｏｎａｌｉｓ）消化道杯状细胞的分布特点进行了分类研究,结果表明：南方鲇消化道杯状细胞的数量从肠前段、肠中段到肠后段,呈现递增趋势,有杯状、囊状和梨形三种不同的形态,ＡＢ反应阳性,ＰＡＳ反应阴性,分泌物主要含酸性粘多糖,属Ⅱ型粘液细胞。     

DAKO-M1在胃癌组织表达的免疫组织化学研究

对９５例胃癌组织进行ＤＡＫＯ－Ｍ１（ＤＡＫＯ－ＣＤ１５）表达的免疫组织化学研究。结果发现,ＤＡＫＯ－Ｍ１在胃癌中的阳性率（８６．３％）显著高于癌旁粘膜和正常胃粘膜（Ｐ＜０．０５和０．００５）。其定位分布有３种类型：即腺腔缘型（Ａ型）、胞膜型（Ｍ型）和胞浆型（Ｃ型）。胃非肿瘤性粘膜组织仅为Ａ型。胃癌３型兼有,高分化癌Ａ型（１８．２％）和Ｍ型（６１．４％）均显著高于低分化癌（Ｐ值均＜０．００５）;低分化癌和粘液癌Ｃ型（各占７２．０％和５３．８％）均显著高于高分化癌（２０．５％）,Ｐ＜０．００５和０．０２５。ＤＡＫＯ－Ｍ１Ｃ型和Ｍ型淋巴结转移率（分别为９７．１％和６９．２％）均显著高于Ａ型（３３．３％）者,Ｐ＜０．００５和０．０５。结果提示,ＤＡＫＯ－Ｍ１是判断胃癌分化水平、恶性程度及预测淋巴结转移的一种有用标志物     

CDX2在胃癌及癌前病变组织中的表达及其临床意义

目的研究CDX2在胃癌及癌前病变组织中的表达及其与临床病理因素之间的关系。方法采用免疫组织化学S-P法检测CDX2在胃癌及癌前病变组织中的表达,采用阿新兰/过碘酸雪夫氏染色(AB/PAS)和高铁二铵/阿新兰(HID/AB)染色对胃黏膜肠化生进行分型。结果 (1)CDX2在正常胃黏膜组织、慢性浅表性胃炎中不表达,CDX2在肠化、异型增生及胃癌中的阳性率(81.7%、50%、48.2%)均明显高于正常胃黏膜组织(P0.05),在肠化组织中的表达明显高于异型增生和胃癌(P0.05),在异型增生和胃癌中的阳性率差异无显著性(P0.05)。CDX2的表达与肠化的分型和异型增生的分级之间均无关系。(2)CDX2在肠型胃癌中的阳性率(67.4%)明显高于弥漫型和混合型胃癌(25.7%、42.9%);CDX2的表达与胃癌分化程度呈正相关,而与淋巴结转移和临床分期呈负相关,差异均有统计学意义。CDX2阳性表达组的五年生存率明显高于阴性表达组(P=0.038);多种变量对胃癌患者术后生存时间影响的分析显示,CDX2的表达和淋巴结转移是影响胃癌预后的独立因素(P0.05)。结论 CDX2可能在胃粘膜肠化生的发生及胃癌的发生发展中起重要作用,可作为胃癌诊断、判断胃癌的恶性程度及患者预后的有用指标。     

米非司酮对大白鼠子宫内膜抗着床作用的组织化学观察

３０只雌性ＳＤ大鼠分为五组,即Ａ组（阴性对照组）,Ｂ组（孕三烯酮阳性对照组１ｍｇ／ｋｇ）,Ｃ组（米非司酮实验组,Ｃｌ１２ｍｇ／ｋｇ,Ｃ２６ｍｇ／ｋｇ,Ｃ３３ｍｇ／ｋｇ）。用组织化学方法观察米非司酮对子宫内膜一氧化氮合成酶（ＮＯＳ）、琥珀酸脱氢酶（ＳＤＨ）、乳酸脱氢酶（ＬＤＨ）、酸性磷酸酶（ＡＣＰ）、硷性磷酸酶（ＡＬＰ）活性和糖原含量的影响。实验结果显示：ＮＯＳ,ＳＤＨ和ＡＬＰ活性较阴性对照组弱,ＬＤＨ和ＡＣＰ活性较阴性对照组强,糖原含量略低于阴性对照组。     

Improved method for mapping gastric intestinal metaplasia using selective histochemical morphometry

A gastrectomy specimen containing two tubular adenomas from a 67-year-old woman was mapped by an improved method using selective histochemical staining. The specimen was divided into 83 blocks measuring 4.0 cm x 0.5 cm. Sections from the blocks were stained with alcian blue (pH 2.5) to detect mucin. Alcian blue-stained fields were easily identified and measured with the aid of a MOP 30 interactive digital image analyzer. The total area of gastric mucosa analyzed in the 83 sections measured 3,270.9 sq mm while the area occupied by alcian blue-stained goblet cells measured 755.9 sq mm (23.1% of the total area). Intestinal metaplasia was present in 46 of 83 blocks. Both the mean size of alcian blue-positive fields per section as well as the number of alcian blue-positive fields per section were significantly larger in the antral zone I and the intermediate zone II than in the fundal zones III, IV and V. The highest proportion of gastric mucosa with intestinal metaplasia was not found around the two gastric adenomas, but elsewhere. There was no significant difference in the proportion of intestinal metaplasia between the greater and lesser curvatures, further challenging the belief that intestinal metaplasia is always greatest along the lesser curvature. The method described will permit future studies of the possible association between intestinal metaplasia and dysplasias and adenocarcinomas of the stomach.     

Genetic factors in the development of gastric precancerous lesions--a role of Helicobacter pylori ?

Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric precancerous alterations. There is a well known predisposition to gastric cancer and the risk of developing it is greater in relatives of patients with familial cases of this malignancy. The aim of this study was to determine the prevalence of gastric precancerous lesions (atrophy and intestinal metaplasia) and their association with Hp infection in first-degree relatives in patients with noncardia gastric cancer. METHODS: Hp status and gastric histology assessed by upper gastrointestinal endoscopy, biopsies from the antral and body region, the rapid urease test and staining for Hp, inflammation, activity, atrophy and intestinal metaplasia (prevalence and grading) were studied in 108 first-degree relatives of patients with noncardia gastric cancer and compared with 73 controls with mild non-ulcer dyspepsia who had no cancer relatives and were examined in the same way. RESULTS: subjects with and without cancer relatives had a similar prevalence of Hp infection (49 vs. 47%). Endoscopy revealed a few asymptomatic duodenal ulcers and small hiatus hernias in Hp positive subjects of both groups. Hp positive relatives of gastric cancer had a markedly higher prevalence of atrophy than those with Hp negativity without cancer relatives (29 vs. 9%) and those with Hp negativity and cancer relatives (29 vs. 3%. Prevalence of intestinal metaplasia was also higher in those with Hp positivity and cancer relatives than in those without cancer relatives (15 vs. 5% and was not present in Hp negative subjects with cancer relatives. Inflammation and activity showed similar scores in subjects with and without cancer relatives with higher scores in both Hp positive groups. The prevalence of precancerous lesions in the relatives of gastric cancer was nearly always confined to those with Hp positivity. One year after eradication the prevalence of atrophy in cancer relatives decreased from 29 to 14%; prevalence of intestinal metaplasia remained without substantial changes. Scores for inflammation and activity were also lower after eradication. CONCLUSIONS: First-degree relatives of patients with gastric cancer have an increased prevalence of gastric precancerous abnormalities which are strongly confined to those with Hp infection. Eradication of Hp in these subjects with cancer relatives reduces the prevalence of precancerous lesions (atrophy) and grades of inflammation and activity. In view of these results, eradication of Hp should be offered to such subjects.     

Expression of UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 in gastric mucosa, intestinal metaplasia, and gastric carcinoma

Aberrant mucin O-glycosylation is often observed in cancer and is characterized by the expression of immature simple mucin-type carbohydrate antigens. UDP-N-acetyl-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6) is one of the enzymes responsible for the initial step in O-glycosylation. This study evaluated the expression of ppGalNAc-T6 in human gastric mucosa, intestinal metaplasia, and gastric carcinomas. Our results showed that ppGalNAc-T6 is expressed in normal gastric mucosa and in intestinal metaplasia. A heterogeneous expression and staining pattern for this enzyme was observed in gastric carcinomas. ppGalNAc-T6 was expressed in 79% of the cases, and its expression level was associated with the presence of venous invasion. Our results provide evidence that ppGalNAc-T6 is an IHC marker associated with venous invasion in gastric carcinoma and may contribute to the understanding of the molecular mechanisms that underlie aberrant glycosylation in gastric carcinogenesis and in gastric carcinoma.     

Nuclear volume in type I gastric intestinal metaplasia

OBJECTIVE: To retrospectively compare nuclear size of epithelial cells in type I intestinal metaplasia (IM) from various pathologic lesions of gastric mucosa. STUDY DESIGN: Endoscopic mucosal biopsies with type I IM from intestinal type gastric carcinoma (n = 25), chronic gastritis (n = 40) and benign ulcer (n = 32) cases were analyzed. After standard fixation, embedding, sectioning, routine hematoxylin and eosin and alcian blue--periodic acid--Schiff reaction (pH 1.0 and 2.5) staining were used for identification of IM. The mean point sampled nuclear intercept was estimated by the original test system and 100x objective at a total magnification of 1,200x. To obtain the mean nuclear volume, the cubed nuclear intercept was multiplied by pi/3. In each case 100 epithelial cell nuclei were analyzed. RESULTS: In type I IM in gastric carcinoma cases there was significantly greater nuclear volume (118.34 +/- 10.32 micron 3) than in type I IM in other pathologic states of gastric mucosa (77.72 +/- 8.58 micron 3). CONCLUSION: The karyometric findings of the present study suggest a difference between type I IM found in benign pathologic states and type I IM found in gastric mucosa surrounding carcinoma, despite morphologic and histochemical similarities. Nuclear volume may be used in early detection of precancerous states of gastric mucosa.     

Effect of Helicobacter pylori infection and eradication on gastric epithelial cell proliferation and apoptosis.

OBJECTIVES: the effect of Helicobacter pylori infection on gastric epithelial cell proliferation and apoptosis is still controversial. Our aim was to evaluate the effect of H. pylori infection on cell kinetic parameters in normal gastric epithelium, gastritis with/without intestinal metaplasia and gastric cancer. PATIENTS AND METHODS: antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58.5+/-14.3 years of age) who underwent routine gastroscopy for upper gastrointestinal symptoms. Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24), and gastric adenocarcinoma (n=8). Fifty-two patients had H. pylori positive gastritis, and success of H. pylori eradication therapy was controlled in 12 cases, all with intestinal metaplasia. To characterize cell proliferation and assess apoptosis, immunohistochemistry [Proliferating Cell Nuclear Antigen (PCNA)], histochemistry [Argyrophil Nucleolar Organizer Regions (AgNOR)], and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling (TUNEL) were used, respectively. RESULTS: both cell proliferation and apoptosis is was higher in chronic gastritis when compared with normal epithelia, but neither PCNA LI (54.79+/-19.1 vs. 53.20+/-20.7) nor AgNOR counts (291.43+/-44.3 vs. 277.8+/-57.54) were different in H. pylori positive versus negative chronic gastritis. A significant positive correlation (P<0.05) was found in this group between PCNA and AgNOR techniques. Apoptosis was significantly higher (P<0.05) in H. pylori positive cases only when intestinal metaplasia was not present. Cell proliferation in intestinal metaplasia decreased to the activity of normal epithelium after successful eradication of H. pylori but remained high if eradication therapy failed. CONCLUSIONS: epithelial cell proliferation does not depend on H. pylori status in chronic gastritis. H. pylori increases apoptosis only in the absence of intestinal metaplasia.     

树突状细胞对胃癌前病变的免疫保护分析

摘要 目的：探究树突状细胞(Dendritic cells,DC)对胃癌的免疫保护作用。方法：选择2016年1月至2018年1月于我院接受治疗的145例胃癌、39例慢性萎缩性胃炎、21例不典型增生、27例肠上皮化生以及20例正常对照组患者为研究对象,分别采集其胃粘膜标本进行染色,记录和比较其胃粘膜中S100⁺、CD4⁺和CD8⁺细胞的数量、平均面积以及平均吸光度,并将胃癌患者分为中分化腺癌(49例)、低分化腺癌(53例)和未分化癌(43例)进行对比。结果：(1)胃癌组、慢性萎缩性胃炎组、不典型增生、肠上皮化生组的胃粘膜S100⁺阳性细胞计数明显高于正常对照组（P<0.05）,胃癌组平均吸光度低于对照组,其他3组平均吸光度显著高于对照组,(P<0.05);胃癌组平均面积与正常对照组相比无差异(P>0.05),其他三组平均面积显著高于对照组（P<0.05）;(2)慢性萎缩性胃炎组、肠上皮化生组、不典型增生组患者CD4⁺细胞数均低于对照组(P<0.05);胃癌组、慢性萎缩性胃炎组、肠上皮化生组患者平均面积均低于对照组(P<0.05);胃癌组、慢性萎缩性胃炎组、不典型增生、肠上皮化生组平均吸光度均低于对照组(P<0.05);(3)慢性萎缩性胃炎组、肠上皮化生组、不典型增生组患者CD8⁺细胞数明显高于对照组(P<0.05),胃癌组稍低于对照组(P>0.05);胃癌组患者平均面积低于对照组(P<0.05);胃癌组患者平均吸光值低于对照组,慢性萎缩性胃炎组、肠上皮化生组患者高于对照组(P均<0.05);(4)随着胃癌分化程度的降低,胃癌患者DC细胞数有降低趋势。结论：胃癌前病变患者胃粘膜中DC数量会显著增多,免疫功能加强,DC细胞数量会随胃癌分化程度的降低而减少,分析其原因与DC细胞能够抑制癌前病变有关。     

Relationship between immunoexpression of mucin peptide cores MUC1 and MUC2 and Lauren's histologic subtypes of gastric carcinomas

Laurèn's system subdivides gastric cancers into an intestinal type and a diffuse type. This histological classification mirrors histogenetic hypotheses according to which the intestinal-type cancer derives from intestinal metaplasia and dysplasia, while the diffuse-type originates directly from gastric mucosa, with or without a preceding non-metaplastic dysplasia. Studies concerning mucins expression in gastric neoplastic and preneoplastic lesions have provided contradictory data concerning such histogenetic relationships. The aim of the present study was to verify whether a correlation between mucins phenotype and Lauren's classification subsists. 40 gastric adenocarcinomas, subdivided, according to Laurèn's classification, into 27 intestinal-type, 10 diffuse-type and 3 unclassified cases, were examined for MUC1 and MUC2 immunohistochemical expression. Intestinal-type carcinomas displayed a MUC1-positive staining in 23/27 cases and a MUC2-positive immunoreaction in 10/27 cases. Diffuse-type carcinomas expressed MUC1 in 3/10 and MUC2 in 8/10 cases, respectively. According to the mucins expression pattern, three phenotypes were identified: the gastric phenotype (MUC1+/MUC2-); the gastro-intestinal phenotype (MUC1+/MUC2+) and the intestinal phenotype (MUC1-/MUC2+). The gastric phenotype was significantly higherin intestinal-type adenocarcinomas, whereas cases showing an intestinal phenotype were significantly more frequent in diffuse-type adenocarcinomas. These findings provide evidence for a lack of correlation between Lauren's classification and MUC1 and MUC2 phenotypes. In particular, the term intestinal-type tumour as referred to gland-forming gastric cancer does not seem to reflect an immunohistochemical phenotype.     

FXR在胃粘膜肠化生及胃癌中的表达及其意义研究

目的:研究FXR在胃炎,胃粘膜肠化生及胃癌组织中的表达,分析其在胃癌发生中的意义。方法:采用免疫组化方法检测FXR在55例胃炎组织,61例胃黏膜肠化生组织及61例胃癌组织中的表达,利用统计学方法 SPSS17.0软件分析其在三种组织中的表达变化,结合文献回顾,分析FXR在胃癌发生中的意义。结果:FXR在胃黏膜肠化生中的表达明显高于胃炎组织(P0.05),而在胃癌组织中,FXR的表达显著低于胃粘膜肠化生组织(P0.05)。结论:FXR是一个潜在的胃癌发生生物标记物,其具体机制有待于进一步探索。     

A method for the quantitation of intestinal metaplasia of the stomach by morphometry

A novel method to quantitate the extent of intestinal metaplasia in gastrectomy specimens is presented. Morphometric measurements of histochemically labeled mucin-producing goblet cells were done in three selected gastrectomies (one having a peptic ulcer, one with adenocarcinoma of the intestinal type, and one with adenocarcinoma of the diffuse type). The sectioning of the gastrectomy specimens was standardized. The results indicated that the intestinal metaplasia was significantly higher in the specimen with adenocarcinoma of the intestinal type (as compared to the other two specimens), both along the lesser and greater curvatures as well as in the fundic area. These quantitative results confirm nonquantitative reports based on subjective visual impressions. This quantitative histochemical method for measuring the actual length as well as the topographical distribution of intestinal metaplasia in resected stomachs will be used in future studies of intestinal metaplasia with the aim of disclosing possible differences among populations with disparate incidences of gastric carcinoma.