食管上皮癌变过程中FAS、FASL、FADD和caspase-8的表达及其意义

目的研究细胞凋亡调控因子FAS、FASL、FADD和caspase-8基因在食管上皮癌变过程中的表达及其意义。方法用免疫组化SP法检测食管黏膜中FAS、FASL、FADD和caspase-8的表达;原位杂交法检测食管黏膜中FADDmRNA和caspase-8mRNA的表达。结果从食管正常黏膜组织到不典型增生和食管癌组织,FAS蛋白表达率呈逐渐下降趋势,FASL蛋白表达率呈逐渐上升趋势,食管癌与正常组织之间差异明显(P<0·05)。高、中分化鳞癌中蛋白阳性表达率显著高于低分化鳞癌(P<0·05)。从食管正常黏膜组织到不典型增生和食管癌组织,FADD和caspase-8蛋白及RNA阳性表达率呈逐渐下降趋势,食管癌与正常黏膜组织之间差异明显(P<0·01);caspase-8蛋白和mRNA在高、中分化鳞癌中的表达率高于低分化鳞癌(P<0·05)。结论FAS与FASL的表达失衡与食管癌的发生、发展有密切关系,并与食管癌的分化和免疫逃避有关。FADD与caspase-8基因表达异常在食管癌的发生、发展中可能起着重要作用。     

同一个体食管和贲门双源癌前病变组织中Rb的表达

目的 探讨同一个体食管鳞状上皮不典型增生(esophageal epithelial dysplasia,EDYS)和贲门腺上皮不典型增生(gastric cardia dysplasia,GDYS)组织中Rb蛋白表达的变化特征及其意义.方法 采用免疫组化ABC法和组织病理学方法,分析河南食管癌高发区30例同一个体同时发生EDYS和GDYS组织中Rb蛋白的表达情况.结果 Rb在EDYS组织中阳性率为70%(21/30),GDYS组织阳性率为80%(24/30),两者阳性率差异无统计学意义(χ~2=0.800,P>0.05);同一个体EDYS和GDYS组织Rb表达有明显一致性(Kappa=0.561,P<0.01),25例(83%,25/30)同时出现EDYS和GDYS组织Rb表达的一致性改变,一致阳性率为67%(20/30),一致阴性率为17%(5/30);EDYS和GDYS组织中Rb的表达相关(P<0.01).结论 Rb在同一个体EDYS和GDYS组织中存在较高的表达一致性改变,进一步提示食管鳞癌和贲门腺癌可能具有相似的发病因素和分子机制.     

p53基因突变与食管贲门多源癌的相关性

目的 探讨食管贲门双源癌组织p53基因突变的特征及其与p53蛋白表达的关系。方法 采用显微切割、PCR、DNA测序和免疫组化ABC法，分析4例食管贲门多源癌p53基因突变和蛋白表达状况。结果 4例食管贲门双源癌中，1例食管鳞癌和贲门腺癌同时发生p53基因突变，并均发生第7外显子231、232密码子的点突变和225、232～233、234密码子的缺失/插入改变。食管鳞癌p53基因突变率为50％(2／4)，贲门腺癌为75％(3／4)。所有检测到的突变均发生在第7和8外显子。食管癌和贲门癌分别有1例p53蛋白阴性表达的患者检测到p53基因突变，食管癌中1例p53蛋白阳性表达患者未检测到基因突变。结论 同一个体食管鳞癌和贲门腺癌组织同时发生相似位点的p53基因突变，提示二者具有相似的发病因素和分子机制，为进一步揭示林州地区相似的食管／贲门癌区域分布特征提供了重要的理论依据和线索。     

食管癌及癌前病变中NF-κB p65/p50蛋白的表达

目的探讨核转录因子NF—κB p65／p50蛋白在食管癌与癌前病变组织的变化特征及其生物学意义。方法采用免疫组化ABC法检测食管癌手术标本的NF—κB p65／p50蛋白表达状况并分析其特征。结果NF—κB p65／p50在正常食管鳞状上皮组织无表达，而在基底细胞增生（38％／32％）、间变（54％／46％）、原位癌（53％／47％）和鳞状细胞癌（69％／62％）均出现不同程度的阳性表达，并随病变进展，阳性表达率明显升高。而基底细胞增生与鳞癌之间表达率差异有显著性（P〈0．05）。NF-κB p65／p50在食管鳞癌中表达有异质性。结论NF—κB p65／p50蛋白表达变化是食管癌和癌前病变组织常见的分子事件，可能在食管鳞癌癌变过程中起一定作用。     

子宫颈鳞状细胞癌中IMP3表达与MVD的相关性分析

目的：分析子宫颈鳞状细胞癌(squamous carcinoma of the cervix, SCC)中胰岛素样生长因子域 mRNA结合蛋白3(insu-lin-like growth factor 域mRNA binding protein 3, IMP3)表达与微血管密度(microvessel density, MVD)的相关性。方法采用免疫组化SP法检测正常子宫颈( normal cervical epithelium, NCE)、低级别子宫颈上皮内瘤变( low-grade cervical intraepithelial ne-oplasia, CIN-L)、高级别子宫颈上皮内瘤变( high-grade cervical intraepithelial neoplasia, CIN-H)和 SCC 组织中 IMP3表达及MVD值,并分析二者与SCC的关系。结果(1) IMP3在NCE、CIN-L、CIN-H和SCC组织中的阳性率分别为0(0/15)、0(0/11)、37.5%(9/24)和86.0%(43/50),差异有统计学意义(字2=53.345,P=0.000);与NCE组相比,CIN-H、SCC组中IMP3阳性率差异均有显著性(P<0.0083);与SCC组相比,CIN-L、CIN-H组中IMP3阳性率差异均有显著性(P<0.0083);(2)子宫颈组织中MVD值随子宫颈病变的进展而增高,差异有统计学意义(F=145.968,P<0.01),各组之间MVD值差异亦具有显著性(P<0.05);(3)SCC组织中IMP3阳性率及MVD值与肿瘤分化程度、肌层浸润深度及淋巴结转移有关(P<0.05),与患者年龄无关(P>0.05),SCC组织中IMP3表达与MVD值具有相关性(rs =0.323,P<0.05)。结论 IMP3在SCC的发生、浸润和转移过程中起重要作用,其异常表达可能与肿瘤的微血管形成有关。     

食管鳞状细胞癌组织中Periostin、VEGF的表达及意义

目的：探讨Periostin、VEGF蛋白在食管鳞状细胞癌组织中的表达及意义。方法采用免疫组化SP法检测130例食管鳞状细胞癌组织及癌旁正常食管黏膜组织中Periostin、VEGF蛋白的表达。结果食管鳞状细胞癌组织中Periostin和VEGF的阳性率明显高于正常食管黏膜组织(P<0．05)。 Periostin表达与食管鳞状细胞癌浸润深度、淋巴结转移有显著相关性(P<0．05)。 VEGF表达与食管鳞状细胞癌分化程度、浸润深度和淋巴结转移有显著相关性(P<0．05)。 Periostin与VEGF表达呈正相关(P<0．05),66例食管鳞状细胞癌患者获得临床随访资料,随访时间1~48个月,Kaplan-Meier生存曲线分析显示,Peri-ostin阳性组患者的生存率明显低于 Periostin阴性组( P<0．05), VEGF阳性组患者的生存率明显低于 VEGF 阴性组( P <0．05)。结论 Periostin与VEGF表达密切相关,联合检测Periostin、VEGF可作为判定食管鳞状细胞癌侵袭、转移能力的客观指标,对食管鳞状细胞癌的预后判断具有重要意义。     

子宫颈腺癌中HPV16/18感染对p16Ink4a、Rb蛋白表达的影响

目的研究16、18型人乳头瘤病毒(HPV16/18)DNA与细胞周期相关蛋白p16Ink4a、Rb在子宫颈腺癌中的表达情况及HPV16/18感染对p16Ink4a、Rb蛋白表达的影响。方法采用组织微阵列技术结合原位杂交和免疫组化EliVision二步法标记检测HPV16/18DNA和p16Ink4a、Rb蛋白在86例子宫颈腺癌、15例子宫颈腺上皮异型增生及24例慢性子宫颈炎组织中的表达。结果子宫颈腺癌组和子宫颈腺上皮异型增生组HPV16/18DNA阳性表达率分别为65·1%和46·7%,均明显高于慢性子宫颈炎组8·3%(P<0·01);p16Ink4a蛋白在子宫颈腺癌组的阳性表达率为74·4%,显著高于慢性子宫颈炎组33·4%(P<0·01)。Rb蛋白在子宫颈腺癌组的阳性表达率为33·7%,低于慢性子宫颈炎组45·8%,但差异无显著性(P>0·05)。HPV16/18感染与子宫颈腺癌的病理分级和组织学类型无关,但与p16Ink4a蛋白表达呈正相关(P<0·05)。p16Ink4a与Rb蛋白表达与子宫颈腺癌的病理分级有关,G2、G3组p16Ink4a阳性表达率明显高于G1组(P<0·05),G3组Rb阳性表达率明显低于G1组(P<0·05)。p16Ink4a表达与子宫颈腺癌组织学类型有明显相关性,子宫内膜样腺癌p16Ink4a阳性表达率明显高于透明细胞腺癌(P<0·05)。结论子宫颈腺癌的发生与HPV16/18感染有关,HPV16/18感染可能影响p16Ink4a、Rb蛋白表达,使子宫颈腺上皮发生癌变并促进恶性发展。     

EZH2蛋白在食管癌组织中的表达

目的观察EZH2蛋白在食管鳞癌和腺癌组织中的表达,探讨EZH2蛋白与侵袭、转移程度不同的食管鳞癌及不同病理分级、组织类型食管癌之间的关系。方法采用免疫组织化学染色法、免疫印迹法,分析检测食管癌标本中EZH2蛋白的表达。结果食管癌组织标本均高表达EZH2蛋白,阳性染色定位于细胞核;部分正常组织、癌旁组织也有弱阳性着色。免疫印迹分析表明,食管鳞癌组织EZH2蛋白的表达明显高于癌旁及正常黏膜组织（P〈0．01）。癌旁组织高于正常黏膜组织（P〈0．05）。浸润、转移性食管鳞癌EZH2蛋白表达明显上调,与未发生浸润、转移的相比,差异有显著性（P〈0．05）。高分化鳞癌EZH2蛋白表达低于中、低分化者;但食管腺癌则相反,高分化腺癌的表达高于中、低分化者。结论EZH2蛋白在食管癌高表达,并与其组织类型、侵袭和转移特性密切相关。     

口腔鳞癌及癌前病变组织中p27、p53蛋白的表达

目的　探讨 p2 7、p5 3蛋白表达在口腔鳞癌发生发展中的意义。 方法　应用免疫组化S P法分别检测 9例口腔正常黏膜 ,11例单纯性增生、2 6例癌前病变及 5 4例鳞癌组织中p2 7、p5 3蛋白的表达。 结果　p2 7蛋白在口腔正常黏膜和单纯性增生组织中呈高表达 ,在癌前病变和鳞癌组织中高 (低 )表达率分别为 6 1 5 % (38 5 % )、2 5 9% (6 1 1% ) ,在鳞癌中阴性表达率为 13% ;p2 7蛋白的表达与鳞癌的组织分化程度、临床分期相关 (P <0 0 5 )。p5 3蛋白在正常黏膜、单纯性增生及轻、中度不典型增生中未见表达 ,在重度不典型增生和鳞癌中可见 2 8 6 %和 4 8 1%的阳性表达 ,二者差异有高度显著性 (P <0 0 1) ;在鳞癌中 p5 3蛋白表达与组织分化程度相关 (P <0 0 5 ) ;p2 7和p5 3表达在鳞癌中呈负相关 (P <0 0 1)。 结论　p2 7蛋白表达的减少在口腔鳞癌的发生发展中起着重要作用 ,并与其预后因素密切相关。p5 3蛋白的表达在癌前病变向鳞癌转变过程中起重要作用。综合分析 p2 7、p5 3表达有助于口腔鳞癌的早期诊断和患者预后的估计。     

食管和贲门癌原发病灶和淋巴结转移灶p53蛋白聚集变…

目的：通过对食管和贲门癌原发病灶和淋巴结转移病灶肿瘤抑制基因ｐ５３变化规律的研究，加深对食管和贲门癌转移发生的分子学基础的了解。方法：采用组织病理学和免疫组织化学（ＡＢＣ）方法，对３１例手术切除的食管和贲门癌原发病灶和转移病灶肿瘤抑制基因ｐ５３蛋白聚集进行比较研究。结果：３１例手术标本中，病理检查发现２４例食管鳞状细胞癌，７例为贲门腺癌。研究表明：２４例食管原发和转移鳞癌中，１１例原发和转移病灶中     

复合因素诱发大鼠胃粘膜癌前病变的动物模型

目的：建立实用有效的动物模型,探讨胃癌前病变与胃癌发生的过程及机制。方法：采用符合国人引起胃癌及癌前病变的多种因素（化学致癌剂ＭＮＮＧ、酒精、胆汁等）进行组合诱发多组大鼠胃癌前病变模型,研究胃癌前病变异型增生（ＧＥＤ）、肠化生（ＩＭ）及胃癌之间的关系。结果：诱发２例腺胃腺癌（均为４５周的ＭＮＮＧ普通组）,３３例腺胃ＧＥＤ,４例十二指肠及小肠腺癌（ＭＮＮＧ加强组３只,ＭＮＮＧ乙醇组１只）等;腺胃ＧＥ     

Immunohistochemical expression of IMP3 and p53 in inflammatory lesions and neoplastic lesions of the gastric mucosa

Aim: Expression of the oncofetal protein insulin like growth factor II messenger ribonucleic acid binding protein 3 (IMP3) has been shown to differentiate between benign and malignant lesions in several tissues. Our aim was to assess the immunohistochemical expression of IMP3 in inflammatory and neoplastic lesions of the gastric mucosa and to determine whether IMP3, alone or in combination with p53, could be used for identifying neoplasia of the gastric mucosa. Methods: IMP3 and p53 immunohistochemistry was performed on 57 cases of gastritis, 28 cases of dysplasia of the gastric mucosa and 63 cases of gastric carcinomas. Focal IMP3 positivity was detected in 86% of non-neoplastic lesions of the gastric mucosa. Using a simple product score (PS), 96% of non-neoplastic lesions of the gastric mucosa were assessed as IMP3(PS) negative. None of the low-grade dysplasia but 83% of high-grade dysplasia were IMP3(PS) positive. Gastric carcinomas showed IMP3(PS) positivity in 65%. Adding p53 to the diagnostic panel increased sensitivity significantly. Conclusion: High-grade dysplasia and gastric carcinomas can be distinguished from low-grade dysplasia and inflammatory lesions of the gastric mucosa with a high specificity and good sensitivity using a combination of the immunohistochemical markers IMP3 and p53.     

河南食管/贲门癌高发区人群食管癌和贲门癌比较基因组杂交分析

目的探讨食管癌/贲门癌高发区人群食管癌和贲门癌染色体基因组变化特征。方法应用比较基因组杂交技术分析37例原发性食管癌和30例贲门癌患者染色体基因组的变化。结果比较基因组杂交发现,食管癌组织染色体8q发生DNA扩增的频率最高(78%),其它依次为3q、5p、6q和7p;3p发生DNA丢失的频率最高(57%),其它依次为8p、9q和11q。贲门癌组织染色体20q发生DNA扩增频率最高(43%),其它依次为6q、8q和6p;17p发生DNA丢失的频率最高(57%),其它依次为19p、1p和4p。结论8q、3q和5pDNA扩增和3p、8p和9qDNA丢失是河南高发区食管癌患者基因组DNA变化特征;而20q、6qDNA扩增和17p、19p、1pDNA丢失可能是河南高发区贲门癌患者基因组DNA变化特征。这些结果为进一步定位筛选和克隆与食管癌/贲门癌相关基因提供了重要的理论信息。     

Promoter hypermethylation of multiple genes in early gastric adenocarcinoma and precancerous lesions

Promoter hypermethylation is an alternative mechanism of gene silencing in human cancers including gastric cancer. To date, several reports on methylation of various genes in gastric cancer have been published. However, most of these studies have focused on cancer tissues or only a single gene. In this study, we determined the methylation frequency of 5 genes, including p16, Runx3, MGMT, DAPK, and RASSF1A, by methylation-specific polymerase chain reaction, in a series of formalin-fixed paraffin-embedded tissues including normal gastric mucosa (n = 20), intestinal metaplasia (n = 14), gastric epithelial dysplasia (n = 27), and early gastric adenocarcinoma (n = 16). Immunohistochemistry was used to determine expression of MGMT and RASSF1A protein. All 20 histologically normal gastric biopsy specimens were methylation-free for all 5 genes. Aberrant hypermethylation of RASSF1A was not detected in any case from intestinal metaplasia to early gastric adenocarcinoma. The methylation rate of the other 4 genes increased with the histological progression from intestinal metaplasia to gastric epithelial dysplasia, to early gastric adenocarcinoma. Methylation was detected in 28.6% of intestinal metaplasia (4/14), in 77.8% of gastric epithelial dysplasia (21/27), and in 87.5% of early gastric adenocarcinoma (14/16). The average number of methylated genes in intestinal metaplasia, gastric epithelial dysplasia, and early gastric adenocarcinoma was 0.43, 1.3, and 1.8, respectively. Concurrent methylation in 3 or more genes was found in 7.1% of intestinal metaplasia, 11.1% of gastric epithelial dysplasia, and 31.3% of early gastric adenocarcinoma. No correlation was found between hypermethylation and other clinicopathologic parameters such as age, sex, Helicobacter pylori infection, and location of lesions. However, we observed a significant association between hypermethylation of p16 and MGMT and elevated serum carcinoembryonic antigen level. No reduction or loss of RASSF1A expression was observed in our study. Weak or loss of MGMT expression was found in 20 lesions and was significantly associated with promoter hypermethylation (P < .01). Our results suggest that promoter hypermethylation of the p16, Runx3, MGMT, and DAPK genes may play an important role in the pathogenesis of gastric precancerous lesions and early gastric adenocarcinoma. Hypermethylation and inactivation of RASSF1A, however, could be a later event in malignant transformation. Further studies are warranted to determine whether the presence of promoter hypermethylation in gastric precancerous lesions is associated with higher risk of subsequent cancer development and how to interrupt the malignant transition from intestinal metaplasia and gastric epithelial dysplasia to early gastric adenocarcinoma by developing some gene-targeting therapies that may reverse aberrant methylation.     

Increased expression of sonic hedgehog and altered methylation of its promoter region in gastric cancer and its related lesions.

The hedgehog (Hh) signaling pathway plays an important role in foregut development, and its activity is increased in various tumors, including those of the digestive tract. Our objective in the present study was to determine the pattern and extent of Sonic hedgehog (Shh) expression in gastric cancer and related lesions as well as the methylation status of its promoter region, in an attempt to clarify the regulatory mechanism of Shh expression. A total of 237 gastric cancers and related lesions (89 carcinomas, 22 high-grade dysplasia, 21 low-grade dysplasia, 47 intestinal metaplasia, 38 chronic gastritis, and 20 normal epithelia) were subjected to immunohistochemical analysis with the Shh monoclonal antibody. The methylation status of Shh was determined by methylation-specific PCR (MS PCR), involving bisulfate treatment of DNA from 150 tissues followed by amplification using specific primer pairs designed by our group. Shh was completely absent in the upper part of normal gastric epithelia (gastric pit cells), and no significant differences were observed among the lower parts of normal epithelia, chronic gastritis, and intestinal metaplasia. However, Shh expression was significantly elevated in neoplastic lesions, such as carcinoma and high low-grade dysplasia, compared to non-neoplastic lesions. In carcinomas, Shh expression was associated with clinical stage, direct tumor invasion, and differentiation of tumor cells. Methylation of the Shh promoter region was frequent in normal gastric pit cells (11/18, 61.1%), but very rare in gastritis (0/18), intestinal metaplasia (0/19), dysplasia (0/10), and carcinoma (1/63, 1.6%), and correlated significantly with expression (P<0.001). Our results suggested that the increased and constitutive Shh expression is implicated in gastric carcinogenesis, and that promoter methylation may be an important regulatory mechanism of Shh expression.     

Adenocarcinoma of the lower esophagus and the esophagogastric junction

This report describes adenocarcinoma in patients with Barrett's esophagus (BE) and adenocarcinoma of the esophagogastric junction (EGJ) and the gastric cardia. Definitions, frequency, and general features of both conditions are described. The macroscopic features and microscopic findings are detailed for invasive adenocarcinoma and superficial (early) adenocarcinoma. Prognosis and follow-up are evaluated using flow cytometry as a factor of prognosis. Precancerous conditions and etiological factors are discussed. In addition, primary adenocarcinoma of the lower esophagus not associated with BE is considered. The precancerous lesions and precancerous markers in BE and in the cardia are examined, including type of dysplasia, histochemical study, and other lines of research.     

不同胃黏膜病变患者的血清胃蛋白酶原变化

目的：探讨胃溃疡、十二指肠球部溃疡、非萎缩性胃炎、萎缩性胃炎、胃癌患者胃蛋白酶原(pepsinogen,PG)Ⅰ、PGⅡ水平和PGⅠ/PGⅡ比值变化。方法：选择2015年1月至2015年10月因消化道症状行胃镜检查的门诊及住院患者共133例,根据胃镜检查及组织病理学结果,将受检者分为5组。非萎缩性胃炎组42例、萎缩性胃炎组33例、胃溃疡组20例、十二指肠球部溃疡组23例、胃癌组15例、比较各组血清PGⅠ、PGⅡ水平。结果：与非萎缩性胃炎组相比,胃溃疡、十二指肠球部溃疡患者PGI明显升高(P<0.05),胃溃疡PGII明显升高(P<0.05),萎缩性胃炎组、胃癌组血清PGⅠ及PGⅠ/PGⅡ水平降低(P<0.05)。结论：血清PGⅠ、PGⅡ水平以及PGⅠ/PGⅡ比值对提高消化性溃疡、胃癌前病变及胃癌的诊断有重要的临床价值。     

Precancerous conditions and epithelial dysplasia in the stomach.

A distinction can be made between a precancerous condition and a precancerous lesion. The former is a clinical state associated with a significantly increased risk of cancer, whereas a precancerous lesion is a histopathological abnormality in which cancer is more likely to occur than in its apparently normal counterpart. Up to the present time atrophic gastritis, gastric ulcer, pernicious anaemia, gastric stumps, gastric polyps, and Ménétrier's disease have all been considered as precancerous conditions and lesions of the stomach. Of these, only atrophic gastritis, pernicious anaemia, gastric stumps, and certain types of gastric polyp can now be regarded as having any really significant malignant potential. The precancerous lesion common to these is epithelial dysplasia which can occur in ordinary (foveolar) gastric epithelium as well as in intestinal metaplasia. The criteria for grading dysplasia in gastric epithelium into mild, moderate, and severe grades are given, and attention is drawn to the problems of differentiating inflammatory or regenerative change from mild dysplasia and intramucosal carcinoma from severe dysplasia. The clinical and epidemiological implications of gastric dysplasia are discussed with suggestions for further research.