159例活检胃粘膜AgNOR分析

应用核仁组成区相关嗜银蛋白(AgNOR)对159例活检胃粘膜标本进行观察分析。提示AgNOR数目多寡对区分活检胃粘膜上皮增生程度,确定活检胃粘膜随访复查的次数及间隔时间,以推断胃粘膜上皮癌变过程及其规律有重要价值。慢性萎缩性胃炎和不典型增生的病例,一部分细胞的银颗粒数目属于癌肿的计数范围,多认为与腺上皮局灶性增生活跃有关。     

胃粘膜异型增生研究进展

在胃癌癌前病变中,最为人们所注意的是胃粘膜上皮异型增生,它是近年来胃癌研究的重要课题。本文拟就这方面研究的某些进展作一综述。一、胃粘膜异型增生的概念胃粘膜异型增生指胃粘膜腺管及上皮的生长偏离了正常的组织结构和细胞分化。其基本特点为:(1)细胞的不典型性;(2)异常分化;(3)粘膜结构紊乱。主要病理组织形态为:(1)上皮细胞呈不典型状态,核呈多形性、嗜碱、浓染,核与胞浆比例增大,细胞极性消失;     

细胞形态测量和DNA含量与AgNOR计数在鼻咽良恶性病变诊断中的应用

 用图像分析仪对正常鼻咽粘膜上皮10例，单纯增生或化生18例，异型增生或化生20例，鼻咽癌24例进行核形态和DNA含量与核仁组成区嗜银蛋白(A_gNOR简称)计数检测，综合各项测量指标进行多元判别分析，结果发现：正常粘膜上皮，单纯增生和鼻咽癌诊断准确率均为100%，异型增生为85%，提示细胞学定量分析是诊断鼻咽良恶性病变的一种比较可靠的方法。异型增生的细胞核形态、DNA含量和A_gNOR计数测量值的个体差异较大，显示异型增生上皮生物学性质的个体差异。     

胃粘膜上皮异型增生的研究状况

胃粘膜的癌变是一漫长而复杂的过程，在胃癌形成之前，常经历多年的癌前病变阶段。胃粘膜上皮异型增生作为一重要的癌前病变已为大量的临床及基础研究所证实。就此领域的研究状况作一综述。１概念、分型及分级胃粘膜上皮异型增生是指胃粘膜腺管及上皮的生长偏离了正常的组...     

活检胃粘膜表面上皮绒毛状异型增生的组织病理学观察

本文对３６例活检胃粘膜表面上皮绒毛状异型增生和４例早期乳头状腺癌的标本进行了组织病理学观察，结果Ⅲ级绒毛状异型增生同乳头状腺癌的关系密切，有向乳头状腺癌过渡的形态。我们认为胃粘膜表面上皮绒毛状异型增生的这一组织病理学改变的形成，是胃粘膜表面上皮细胞受致突／致癌变物质的不断作用，失去正常分化，而出现由异型增生到癌变过程中的过渡阶段，是乳头状腺癌的重要癌前期病变。胃粘膜表面上皮绒毛状异型增生多合并慢性萎缩性胃炎。     

早期胃癌及其癌前病变的形态定量分析

多数学者认为胃粘膜上皮异型增生是重要的癌前病变。临床病理对胃粘膜异型增生的判定存在着较强的主观性,这主要是缺乏更客观的判定指标,因此研究判断异型增生级别和良恶性的客观指标是一项非常重要的课题。用形态定量方法研究界型增生级别已有文献报道,但尚缺乏早期胃癌的形态定量资料。本文应用图象分析仪对早期胃癌粘膜增生和癌区作了形态定量研究,探讨胃粘膜异型增生和癌变之间的关系,以及胃癌发生及发展的规律。     

胃癌核仁组成区相关嗜银蛋白的研究

应用核仁组成区相关嗜银蛋白(AgNOR)染色技术,对56例胃粘膜活检标本进行观察。其中胃正常粘膜6例,不典型增生18例,胃高分化腺癌18例,低分化腺癌14例,光镜定量显示,胃正常粘膜、不典型增生和胃癌上皮AgNOR数目有显著差异,胃癌组(高分化与低分化)上皮AgNOR数日显著高于正常粘膜和不典型增生组。但重度不典型增生组和胃癌组AgNOR均值有一定程度重叠。结果提示核仁组成区相关嗜银蛋白技术对胃良恶性病变的诊断有益。     

胃粘膜异型增生上皮p53蛋白表达的临床意义

采用免疫组化方法，对２４例常规胃镜活检的胃粘膜异型增生上皮的ｐ５３蛋白表达进行检测，并做１～２４个月的随访研究。结果表明，ｐ５３蛋白阳性的异型增生上皮的癌检出率为５７．１％（４／７），其中２例为早期胃癌，而ｐ５３阴性的异型增生上皮的癌检出率为１１．８％（２／１７），两者有显著性差异（Ｐ＜０．０５）。结果提示，胃粘膜上皮ｐ５３蛋白表达是一项恶性生物学指标，可作为早期诊断及鉴别诊断胃癌的标志     

胃粘膜不典型增生核仁组成区嗜银蛋白的图像分析研究

本文用石蜡包埋组织切片标本细胞核仁组成区嗜银蛋白(AgNOR)的银染方法,对正常及各级不典型增生胃粘膜上皮细胞及胃癌间AgNOR颗粒数量变化的定量研究并用图像分析技术,对上述各组石蜡切片标本的细胞AgNOR进行了定量分析,以进一步探讨其在胃粘膜病变间的鉴别诊断意义.1 材料和方法 材料全部为西京医院病理科存档的胃粘膜活检蜡块.包括高分化腺癌20例,重度不典型增生19例,中度不典型增生25例,轻度不典型增生20例,正常胃粘膜24例.     

核仁组成区测定对胃癌和癌前病变诊断上的意义

应用核仁组成区嗜银蛋白染色法(AgNoRs),对130例胃粘膜病变进行定量测定。结果表明单纯肠上皮化生、异型增生和分化型腺癌的每核平均AgNoRs颗粒量,随病变程度加重而递增。除重度异型增生与腺癌明显交叉重叠外,各组之间皆有非常显著性差异(P<0.01)。因此,我们认为AgNoRs测定,可作为胃癌和癌前病变诊断、分级上较客观的辅助性定量指标。高活性rRNA的出现可能是重要癌变标志。     

胃异型增生上皮、胃腺癌组织中神经内分泌与p53蛋白的检测

目的　探讨胃异型增生上皮、胃腺癌组织中神经内分泌和 p5 3蛋白的表达及意义。 方法　应用免疫组织化学法检测10例正常胃黏膜、63例癌旁低度异型增生、2 6例高度异型增生及相应胃腺癌组织中嗜铬粒蛋白A (CgA )、突触素 (Syn)、神经元特异性烯醇化酶 (NSE)和p5 3蛋白的表达。结果　癌旁低度异型增生、高度异型增生及相应胃腺癌组织中 ,CgA、Syn、NSE和 p5 3蛋白阳性表达率均有非常显著性差异 (P <0 .0 1)。结论　胃异型增生上皮和胃腺癌伴神经内分泌是 1种常见的现象 ,它和 p5 3蛋白在胃腺癌的发生发展中的作用可能有所不同     

The histogenesis of adenocarcinoma of the gallbladder

A prospective study of 277 cholecystectomy specimens for evidence of isolated epithelial dysplasia of gallbladder mucosa is presented. In addition, 15 cases of primary adenocarcinoma of the gallbladder are retrospectively reviewed with particular reference to the presence of metaplasia and dysplasia adjacent to the infiltrating tumor, in order to establish the relationship between metaplasia, isolated epithelial dysplasia, and adenocarcinoma of the gallbladder. Only one case of isolated epithelial dysplasia was found in the 277 cholecystectomy specimens, and this arose within focal incomplete intestinal metaplasia. In the 15 cases of adenocarcinoma of the gallbladder, benign antral and/or incomplete intestinal metaplasia was found adjacent to the tumor in 11 cases. In 10 cases, dysplasia of this metaplastic epithelium was found in continuity with the tumor. The authors conclude that the most common pathway to adenocarcinoma is via dysplasia of metaplastic gallbladder epithelium.     

胃癌及癌前病变原位DNA含量与核仁组成区嗜银蛋白定量分析的相关性研究

本文用图像分析的方法对正常胃粘膜、轻、中、重度异型增生、管状腺癌及低分化腺癌共30例石蜡切片标本的细胞核仁组成区嗜银蛋白(AgNOR)和细胞核DNA含量进行了定量检测,并进行了两者的相关性研究。结果显示AgNOR颗粒数量及DNA含量均随病变程度加重而增加,AgNOR数量与DNA含量、超二倍体及超四倍体细胞百分数、DNA直方图倍体类型之间有明显的相关性(r=0.8811,0.7288,0.8606,0.8793);提示AgNOR数量与DNA含量的变化对胃癌前病变的判断与研究具有相近的意义。与细胞核DNA含量检测相比,AgNOR计数分析具有染色简便,易于推广的优点,是胃癌及癌前病变研究中一项新的、实用的参考指标。     

Claudin-4, mitogen-activated protein kinase kinase 4, and stratifin are markers of gastric adenocarcinoma precursor lesions.

Approximately 23,000 new gastric cancer cases and 12,000 associated deaths occur annually in the United States. Intestinal metaplasia and gastric epithelial dysplasia are precursor lesions to gastric adenocarcinoma, but are not readily detectable clinically, radiographically, or endoscopically. A noninvasive method of precursor detection would require the ability to distinguish precursor lesions from adjacent normal mucosa. In search of such markers, tissue microarrays were prepared for 133 patients of resected gastric adenocarcinoma. Tissue microarrays contained primary cancer, normal stomach, intestinal metaplasia, and gastric epithelial dysplasia and were probed with antibodies against nine potential markers that were either identified in a database of genes overexpressed in gastric adenocarcinoma or were already of interest to our laboratory: claudin-4, mitogen-activated protein kinase kinase 4 (MKK4), 14-3-3sigma (stratifin), S100A4, mesothelin, fascin, topoisomerase IIalpha, HER-2/neu, and epithelial growth factor receptor. Three markers discriminated gastric adenocarcinoma precursor lesions from normal gastric mucosa. Claudin-4 expression was present in 36 intestinal metaplasia lesions (100%) and 14 gastric epithelial dysplasia lesions (100%), but in only 16 normal stomach samples (15%). MKK4 expression was present in 24 intestinal metaplasia lesions (89%) and 12 gastric epithelial dysplasia lesions (100%), but in only 6 normal stomach samples (8%). Stratifin expression was present in 29 intestinal metaplasia lesions (97%) and 8 gastric epithelial dysplasia lesions (100%), but in only 2 normal stomach samples (3%). Sensitivity and specificity for detection of the precursor lesion intestinal metaplasia were 100% and 85%, respectively, for claudin-4; 89% and 92%, respectively, for MKK4; and 97% and 97%, respectively, for stratifin. In primary cancers, 123 of 125 (98.4%) were positive for claudin-4, 116 of 126 (94%) for MKK4, and 111 of 120 (92%) for stratifin. In conclusion, claudin-4, MKK4, and stratifin immunolabeling detects precursor lesions of gastric adenocarcinoma that are otherwise clinically, radiographically, and endoscopically inapparent. These findings may prove useful in the diagnosis and therapeutic targeting of gastric adenocarcinoma precursor lesions.     

大肠腺瘤和腺癌组织中Survivin的表达及其意义

目的:研究Survivin在大肠腺瘤和腺癌组织中的表达及其意义。方法:SP法检测大肠腺瘤50例(管状腺瘤35例,绒毛状腺廇9例,混合腺廇6例)和大肠腺癌89例组织中Survivin表达情况,正常大肠黏膜组织20例作为对照。结果:在正常大肠黏膜组织、腺瘤和大肠腺癌中,Survivin的阳性表达率分别为10.0%(2/20)、26.0%(13/50)和75.3%(67/89);随腺瘤不典型增生程度增高,Survivin的表达也随之明显增高,P=0.019。Survivin的表达随大肠腺瘤分化程度的降低而升高[高、中和低分化组阳性表达率分别为65.0%(26/40)、86.0%(37/43)和100%(6/6)]。伴有淋巴结转移组大肠腺癌Survivin阳性表达率85.2%(52/61)明显高于无淋巴结转移组53.6%(15/28),P=0.003。在生存时间≥2年的大肠腺癌中,阳性表达率为73.7%(14/19),在<2年组中为64.7%(11/17),两者差异无统计学意义,P=0.41。结论:正常大肠黏膜、大肠腺瘤和大肠腺癌中Survivin的阳性表达逐步增高。随大肠腺瘤不典型增生程度增高,Survivin的表达也随之明显增高。Survivin的表达随大肠腺癌分化程度的降低而升高。伴有淋巴结转移组大肠腺癌Survivin表达的阳性率明显高于与无淋巴结转移组。     

Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues

This study characterizes the morphologic features and the endogenous fluorescence in the stratified squamous epithelia of the 7,12-dimethylbenz(a)anthracene-treated hamster cheek pouch model of carcinogenesis using multiphoton laser scanning microscopy (MPLSM). MPLSM allows high-resolution, three-dimensional image data to be collected deeper within thick tissue samples with reduced phototoxicity compared with single-photon imaging. Three-dimensional image stacks of normal (n = 13), precancerous (dysplasia, n = 12; carcinoma in situ, n = 9) and cancerous tissue [nonpapillary squamous cell carcinoma (SCC), n = 10, and papillary SCC, n = 7] sites in the hamster cheek pouch were collected in viable, unsectioned tissue biopsies at a two-photon excitation wavelength of 780 nm. Five features were quantified from the MPLSM images. These included nuclear density versus depth, keratin layer thickness, epithelial thickness, and the fluorescence per voxel in the keratin and epithelial layers. Statistically significant differences in all five features were found between normal and both precancerous and cancerous tissues. The only exception to this was a lack of statistically significant differences in the keratin fluorescence between normal tissues and papillary SCCs. Statistically significant differences were also observed in the epithelial thickness of dysplasia and carcinoma in situ, and in the keratin layer thickness of dysplasia and SCCs (both nonpapillary and papillary). This work clearly shows that three-dimensional images from MPLSM of endogenous tissue fluorescence can effectively distinguish between normal, precancerous, and cancerous epithelial tissues. This study provides the groundwork for further exploration into the application of multiphoton fluorescence endoscopy in a clinical setting.     

P21蛋白和细胞核DNA含量在胆囊炎后性壁肥厚型腺癌中的研究

对102例慢性胆囊炎壁肥厚和12例慢性胆囊炎后性壁肥厚型腺癌，采用ras癌基因P21蛋白和细胞核DNA含量进行观察。结果发现P21蛋白在慢性胆囊炎壁肥厚中随异型增生程度增加而递增，重度的慢性胆囊炎壁肥厚与胆囊炎壁肥厚型腺癌相接近。细胞核DNA含量在慢性胆囊炎壁肥厚中相对倍体均值增高，重度的慢性胆囊炎壁肥厚与胆囊炎后性壁肥厚型腺癌无显著性差异（P＞0．05）。提示慢性胆囊炎壁肥厚腺上皮增生、异型，最后发展为胆囊炎后性壁肥厚型腺癌。     

Gastrointestinal carcinoma-associated antigen detected by a monoclonal antibody in dysplasia and adenocarcinoma associated with chronic ulcerative colitis

Colorectal tissue specimens from 13 patients with chronic ulcerative colitis, of whom all had epithelial dysplasia and 2 had adenocarcinoma, were tested for the presence of gastrointestinal carcinoma-associated antigen (GICA), using an immunoperoxidase technique with a monoclonal antibody (MAb) against this antigen. GICA was present in the formaldehyde-fixed and paraffin-embedded sections of dysplastic and cancer tissue but absent from normal or hyperplastic epithelium. However, the pattern and extent of staining with the antibody did not correlate with the degree of dysplasia, i.e., "mild" dysplasia was often positive, and "severe" dysplasia was sometimes negative. Changes classified as "indefinite for dysplasia but probably negative" were variable in their expression of GICA. The adenocarcinomas were selectively labelled within cell clusters. In contrast, ulcerative colitis (UC) patients with severe inflammatory changes but with no detectable dysplasia were negative for GICA. GICA could be eluted from paraffin blocks of dysplastic tissue and biochemically characterized as a glycolipid. The detection of this antigen might be a useful complement to morphological examination in discriminating between precancerous and benign epithelial lesions of the colon.     

Spontaneous squamous carcinoma of the esophagus in chickens

Histologic preparations from 149 gullets from chickens from the Linxian county (Henan province, northern China) having intraepithelial neoplasms or invasive carcinomas were reviewed. Invasive squamous cell carcinomas were found in 134 animals and invasive adenocarcinomas in seven. The remaining eight specimens had only intraepithelial neoplastic lesions: four with low-grade dysplasia and four with high-grade dysplasia (one with carcinoma in situ). The degree of differentiation in invading tumors was as follows: of the 134 invasive squamous carcinomas, two were highly differentiated, 125 moderately differentiated, and 22 poorly differentiated. All seven adenocarcinomas were moderately differentiated. In 97 of the 149 invasive carcinomas, intraepithelial neoplastic lesions were observed near the tumors: in 96 adjacent to invasive squamous carcinoma, and in one in the glandular epithelium adjacent to invasive adenocarcinoma. In the remaining 44, only invasive carcinoma was present. Epithelial buds bulging into the stroma were present in intraepithelial neoplastic lesions: in 71.8% in low-grade dysplasias adjacent to invasive carcinoma and in 94.4% in high-grade dysplasias adjacent to invasive carcinoma. Moreover, two of the four animals with low-grade dysplasia exclusively, and the four with high-grade dysplasia (one with carcinoma in situ) also had epithelial buds. In two specimens, invasive carcinoma was found to originate at the tip of the irregular buds with dysplasia. Similar histologic events have been found in chemically induced squamous esophageal carcinomas in rodents and in early squamous carcinoma in humans. It is therefore suggested that there is a close association between the degree of squamous cellular atypia, the formation of epithelial buds, and the progression toward invasive carcinoma in the esophagus.