胃癌和胃粘膜异型增生核仁组织区嗜银蛋白定量和形态研究

目的探讨核仁组织区嗜银蛋白（ＡｇＮＯＲ）染色技术在胃癌、癌前病变、慢性胃炎中鉴别诊断价值和意义。方法应用ＡｇＮＯＲ染色技术，观察１３２例胃良恶性病变和癌前病变细胞核中ＡｇＮＯＲ颗粒含量和形态。结果胃癌、胃粘膜异型增生、慢性胃炎三组间细胞核内ＡｇＮＯＲ颗粒均数差异非常显著（Ｐ＜０．０１），正常胃壁粘膜与慢性胃炎ＡｇＮＯＲ颗粒均数无明显差异（Ｐ＞０．０５）。胃癌和胃粘膜异型增生ＡｇＮＯＲ颗粒形态以弥散型为主，而慢性胃炎和正常胃粘膜以核仁型为主。结论细胞核内ＡｇＮＯＲ颗粒含量和分型对于区别胃良恶性及癌前病变有重要参考价值。     

前列腺癌AgNOR计数与DNA含量测定的意义

作者应用银染色技术对３０例前列腺癌、２０例前列腺增生症组织中的核仁组成区相关嗜银蛋白（ＡｇＮＯＲ）进行检测，并采用图像分析技术测定其ＤＮＡ含量。结果显示，在前列腺癌组织中，ＡｇＮＯＲ计数与ＤＮＡ含量均明显高于前列腺增生症组织（Ｐ＜０．００１）；肿瘤分化越差，ＡｇＮＯＲ计数和ＤＮＡ含量越高，并且与患者预后相关（Ｐ＜０．００１）；ＡｇＮＯＲ计数与ＤＮＡ含量呈明显的正相关（Ｐ＜０．０１）。结果提示ＡｇＮＯＲ计数与ＤＮＡ含量可作为反映前列腺癌生物学行为的指标。     

肺鳞癌及癌前病变的核仁组成区嗜银蛋白测定分析

本文应用ＡｇＮＯＲｓ染色法，对肺鳞癌癌变不同阶段的支气管活检粘膜组织其８５例石蜡切片作定量分析。结果表明，在这一癌变过程中，ＡｇＮＯＲ颗粒既有数量的增加，也有形态的异常，组织学分级与ＡｇＮＯＲ／核均数及畸异型胞核呈正相关ｒ＝０．９１０和０．９０７，Ｐ值均〉０．０５，与核仁型胞核负相关ｒ＝（－０．９６２，Ｐ〈０．００５）。对ＡｇＮＯＲ的数量及颗粒形态的分计数综合分析，试图为肺鳞癌和癌前病变的论断及其     

食管鳞癌组织AgNOR计数与DNA倍的关系

本文应用ＡｇＮＯＲ技术对２０例食管鳞癌手术切除标本中癌细胞核内ＡｇＮＯＲ进行计数，同时运用流式细胞分析技术测定其ＤＮＡ指数及Ｓ期细胞百分率，并与ＡｇＮＯＲ计数进行比较，结果显示：食管鳞癌细胞核内平均ＡｇＮＯＲ数目与Ｓ期细胞百分率呈明显正相关（ｒ＝０．７３）。而ＤＩ与ＡｇＮＯＲ计数无明显相关关系（ｒ＝０．３０）。     

核仁形成区相关嗜银蛋白与上皮细胞增殖

应用放射自显影和银染技术检测Ｗｉｓｔａｒ大鼠食管和小肠上皮细胞增殖状态结果表明：食管底层细胞３Ｈ－ＴｄＲ标记率０．２１，ＡｇＮＯＲｓ数目１．７７，高于浅层细胞的０．０５和１．４０（Ｐ＜０．００５）。肠腺上皮细胞３Ｈ－ＴｄＲ标记率为０．７５，ＡｇＮＯＲｓ数目２．７７，高于绒毛上皮细胞的０．５０和２．０５（Ｐ＜０．００１）。３Ｈ－ＴｄＲ标记率和ＡｇＮＯＲｓ数目在底层细胞（ｒ＝０．８６）、浅层细胞（ｒ＝０．８８）、肠腺细胞（ｒ＝０．９１）和绒毛细胞（ｒ＝０．６７）均呈直线密切正相关。提示：上皮细胞中ＡｇＮＯＲｓ数目与ＤＮＡ合成同步增长；ＡｇＮＯＲＳ数目准确标示了不同增殖状态细胞群体，是反映细胞增殖水平的敏感指标。     

食管鳞癌组织AgNOR计数与DNA倍体的关系

本文应用ＡｇＮＯＲ技术对２０例食管鳞癌手术切除标本中癌细胞核内ＡｇＮＯＲ进行计数，同时运用流式细胞分析技术测定其ＤＮＡ指数（ＤＩ）及Ｓ期细胞百分率，并与ＡｇＮＯＲ计数进行比较。结果显示：食管鳞癌细胞核内平均ＡｇＮＯＲ数目与Ｓ期细胞百分率呈明显正相关（ｒ＝０．７３）。而ＤＩ与ＡｇＮＯＲ计数无明显相关关系（ｒ＝０．３０）。     

宫颈良,恶性病变核仁组成区蛋白定量与宫颈癌预后的研究

应用核仁组成区蛋白嗜银（ＡｇＮＯＲ）技术，对１０９例宫颈良、恶生病变进行了ＡｇＮＯＲ定量研究。结果表明：１．慢性宫颈炎、宫颈非典型增生、宫颈鳞癌三种病变的ＡｇＮＯＲ均值有显著差异（Ｐ〈０．０１）。２．宫颈鳞癌组织学Ｉ级ＡｇＮＯＲ计数低于组织学Ⅱ级（Ｐ〈０．００１）。３．随访１０年以上的７３例宫颈鳞癌患才，核仁组成区蛋白高均值组（≥５）的患才生存时间显著短于低均值组（〈５）（Ｐ〈０．０５），１０年生     

大肠癌细胞DNA、AgNORs定量研究──两者相关性及预后意义的探讨

应用ＡｇＮＯＲｓ染色技术，对６３例大肠癌的ＡｇＮＯＲｓ颗粒进行了计数研究。其中３８例同时进行肿瘤细胞核ＤＮＡ含量静态测定。结果表明，大肠癌细胞ＡｇＮＯＲｓ数量与其ＤＮＡ含量之间有明显相关性（Ｐ＜０．０ｌ）。ＤＮＡ含量和ＡｇＮＯＲｓ计数愈低，肿瘤分化愈好，患者预后愈好；反之，ＤＮＡ含量和Ａｇ－ＮＯＲｓ计数愈高、肝瘤分化愈差，患者预后愈差。表明ＡｇＮＯＲｓ计数，ＤＮＡ含量检测均可作为大肠癌分级、判断预后的参考指标。     

AgNORs检测对胃粘膜良、恶性病变的诊断价值

为探讨ＡｇＮＯＲｓ变化对胃粘膜良、恶性病变的诊断价值，应用银染技术对５０例胃粘膜良、恶性病变进行ＡｇＮＯＲｓ计数，其中正常胃粘膜４例，萎缩性胃炎５例，异型增生９例，胃癌３２例（高分化型腺癌８例，低分化型腺癌１８例，未分化癌６例）。结果：正常胃粘膜、萎缩性胃炎和异型增生细胞核内ＡｇＮＯＲｓ颗粒均数，分别与胃癌各型癌细胞核内均数比较均有显著性差异（Ｐ＜０．０１）。可以认为这种方法有助于区别胃粘膜良、恶性病变及其预后的判断。     

宫颈良、恶性病变核仁组成区蛋白定量与宫颈癌预后的研究

应用核仁组成区蛋白嗜银（ＡｇＮＯＲ）技术，对１０９例宫颈良、恶性病变进行了ＡｇＮＯＲ定量研究。结果表明：１．慢性宜颈炎、宫颈非典型增生、宫颈鳞癌三种病变的ＡｓＮＯＲ均值有显著差异（Ｐ＜０．０１）。２．宫颈鳞癌组织学１级ＡｇＮＯＲ计数低于组织学Ⅱ级（Ｐ＜０．００１）。３．随访１０年以上的７３例宫颈鳞癌患者，核仁组成区蛋白高均值组（≥５）的患者生存时间显著短于低均值组（＜５）（Ｐ＜０．０５），１０年生存率分别为１８％与４６％。作者认为，ＡｇＮＯＲ计数可作为一种新的肿瘤定量指标，在宫颈良、恶性病变的鉴别诊断、选择最佳治疗方案、推测宫颈癌预后等方面具有重要的临床价值。     

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。     

Antigen MG7 in gastric cancer and gastric precancerous lesions

Earlydetectionandearlydiagnosisofgastriccancerareessentialtodecreasethemortalityandincreasesurvivalrateofgastriccancer.TheZhuangheregioninLiaoningProvinceisahighriskareaofgastriccancerandanimportantresearchbaseforgastriccancerpreventionandtreatmentinChina[1].AlargescalescreeningofgastriccancerinthisareawascarriedoutbytheCancerInstituteofChinaMedicalUniversitypreviously.Inthepresentstudy,thegastricmucosasamplesfromthescreeningwereusedtoinvestigatethedynamicexpressionofgastriccancer-associat…     

胃粘膜肠化生细胞DNA含量测定与增殖状态分型的关系

目的：探讨胃粘膜肠化生细胞ＤＮＡ含量与增殖状态分型、硫酸化粘液分泌状况之间的关系。方法：采用ＤＮＡ图像分析技术测定３９４例胃粘膜活检及外科手术标本中细胞ＤＮＡ含量,并对１８７例伴肠化生慢性萎缩性胃炎作免疫组化与粘液组化套染,进行肠化生增殖状态分型。结论：胃粘膜出现肠化生和异型增生、癌变时,出现异倍体细胞且百分率显著增高（Ｐ＜０．０１）;高增殖型肠化生中异倍体细胞的百分率显著高于中、低增殖型肠化生（Ｐ＜０．０１）。结论：提示高增殖型肠化生与胃癌的发生密切相关。     

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.     

CDX2基因在肠型胃癌发展过程中的研究进展

果蝇相关同源异型框转录因子2(CDX2)在肠上皮黏膜细胞的发育及保持形态、结构特征中起重要作用.肠型胃癌经历了正常胃黏膜、肠上皮化生到异型增生再到肠型胃癌的多步骤、多阶段逐渐发展的过程.迄今越来越多的研究发现,CDX2基因的异常表达与胃黏膜肠上皮化生和异型增生以及胃癌的发生密切相关.     

Pericryptal fibroblast sheath in intestinal metaplasia, dysplasia and carcinoma of the stomach

Objective  

To investigate the existence of pericryptal fibroblasts sheath (PCFS) in normal gastric mucosa, intestinal metaplasia (IM), indefinite for dysplasia (I-Dys), low grade dysplasia (L-Dys), high grade dysplasia (H-Dys) and gastric cancer (GC), and its association with gastric carcinogenesis.     

人胎盘型谷胱甘肽S转移酶在胃癌组织中的表达与基因甲基化关系的研究

目的：研究胃癌组织中ＧＳＴ－π的表达与其基因甲基化状态的关系。方法：应用Ｓ－Ｐ法检测１１６例胃癌和５３例胃癌前病变的ＧＳＴ－π表达和限制性内切酶及ＰＣＲ、Ｓｏｕｔｈｅｒｎ印迹方法检测１４例胃癌及其相应正常胃粘膜ＧＳＴ－πＤＮＡ５′端调控区ＣＣＧＧ特定位点的甲基化水平。结果：ＧＳＴ－π阳性率,正常胃粘膜１０％（４／３９）,胃癌７７％（８９／１１６）,肠上皮化生７６％（１９／２５）,不典型增生８９％（２５／２８）。ＧＳＴ－π在胃癌及癌前病变中的表达较正常胃粘膜增高（Ｐ＜００１）。胃癌组织中ＧＳＴ－π基因较正常胃粘膜呈现高度去甲基化（Ｐ＜００１）,胃癌ＧＳＴ－π基因５′端调控区低甲基化与其ＧＳＴ－π表达增加呈相关性（Ｐ＜００５）。结论：ＧＳＴ－π在胃癌及癌前病变中的表达与胃癌的发生发展密切相关,ＧＳＴ－π可作为胃癌的肿瘤相关抗原;ＧＳＴ－π基因５′端调控区低甲基化可能是ＧＳＴ－π高表达的分子机理。     

抗胃癌单克隆抗体MG7和MGd—1在胃癌中的分布

Two murine monoclonal antibodies MG7 and MGd-1 were used to label tissue specimens of gastric cancer and precancerous lesions with ABC method. The antigen to MG7 had a higher specificity to gastric cancer. The positive rate was 47.5% in early gastric cancer, 57.1% in advanced. But it was lower in precancerous lesions: 12.5% in dysplasia, 5% in intestinal metaplasia, 40% in adenoma. In addition, the stain was weaker than in gastric cancer. The antigen to MGd-1 had a higher positive rate in gastric cancer. It was 65.0% in early cancer, 88.6% in advanced. The positive rate was also high in precancerous lesions: 25.6% in intestinal metaplasia, 30.0% in adenoma, 57.5% in dysplasia. MG7 and MGd-1 did not react with the normal tissue and embryo gastric mucosa. Histologically, they show the strongest reaction to signet ring cell cancer.