胃癌组织p170基因表达的研究

为研究糖蛋白ｐ１７０基因在胃癌中的表达，对８０例内镜活检及术后确诊的胃癌组织用抗生物素—过氧化酶复合物进行免疫组化染色研究。结果，胃癌组织中ｐ１７０基因表达均增强，其阳性率达６６％及７１％，并且阳性表达与胃癌组织学类型及分化程度有一定关系，管状腺癌中ｐ１７０阳性表达率高，高、中分化腺癌高于低分化、粘液腺癌、乳头状腺癌等。其分布形式基本相似，主要位于细胞浆内，其次在细胞膜内，细胞核内偶见，癌旁组织也有较强阳性表达。在转移淋巴结组中阳性表达显著高于非转移淋巴结组，提示ｐ１７０与胃癌转移密切相关。结果显示糖蛋白ｐ１７０在胃癌组织中的表达有可能成为一种新的肿瘤标志物。     

肿瘤抑制基因p53及p16与胃癌生物学行为的关系

目的探讨肿瘤抑制基因ｐ５３和ｐ１６异常与胃癌生物学行为的关系．方法采用免疫组化ＡＢＣ法检测５８例原发性胃癌（男３８例，女２０例，年龄３７岁～７６岁），Ｐ５３和Ｐ１６蛋白的表达变化．所有组织均新鲜取材，并迅速用８５０ｍｌ／Ｌ酒精固定，石蜡包埋，连续切片．结果受检组织中ｐ５３和ｐ１６阳性表达率分别为５１７％（３０／５８）和４８３％（２８／５８）．Ｐ５３蛋白在低分化胃癌（７００％）、进展期胃癌（５６９％）、淋巴结阳性胃癌（７４１％）中的表达率高于相应的高分化、早期、淋巴结阴性胃癌的表达率（２７３％，１４３％，３２３％）（Ｐ＜００５），且ｐ５３高表达多见于弥散型胃癌（同肠型胃癌比）、累及浆膜的胃癌也较局限于粘膜层的胃癌有更高的Ｐ５３蛋白表达（Ｐ＜００５）；Ｐ１６蛋白表达与胃癌大多数生物学行为无明显关系，但其在淋巴结阳性胃癌中的表达率（３３３％），低于淋巴结阴性胃癌中的表达率（６１３％）；相关性分析显示；ｐ５３阳性组织大多伴有Ｐ１６蛋白阳性表达（Ｐ＜００５）．结论Ｐ５３蛋白异常表达对胃癌生物学行为有广泛影响，Ｐ１６蛋白表达缺失可能是胃癌淋巴结转移的重要促发因素．     

共信号分子B7-H4在人肺腺癌中的表达及临床意义

目的研究共信号分子B7-H4在人肺腺癌组织中的表达及临床意义。方法收集2013年10月-2014年10月手术切除的肺腺癌患者肺癌组织标本94份,正常肺组织标本20份,应用免疫组织化学法,分别检测组织标本中B7-H4的表达水平。结果 B7-H4在20份正常人肺组织中表达较低,在94份人肺腺癌组织中的阳性表达率为67.32%,在合并有淋巴结转移的肺腺癌组织中B7-H4的阳性表达率为73.24%。低分化组肺腺癌组织B7-H4阳性表达率(84.82%)明显高于中分化组(77.38%)和高分化组(62.51%)。结论共信号分子B7-H4在肺腺癌组织中表达上调,有可能成为评价肺腺癌分化程度和淋巴结转移的指标之一。     

胃癌组织中β-catenin及nm23H1的表达及其临床意义

目的: 探讨β-catenin和nm23H1在胃癌组织中的表达及其与侵袭、转移的关系. 方法:采用免疫组织化学方法检测63例胃癌及30例浅表性胃炎组织中β-catenin及nm23H1的表达情况.结果: 胃癌组织中β-catenin阳性表达率为49.2%, nm23H1的阳性表达率为55.6%, 均明显高于浅表性胃炎, 而且低分化组及淋巴结转移阳性组β-catenin阳性率明显高于高分化组及淋巴结转移阴性组(63.3% vs 33.3%, P<0.05;60.5% vs 32.0%, P<0.05), 低分化组及淋巴结转移阳性组nm23H1的阳性率明显低于高分化组及淋巴结转移阴性组(40.0% vs 73.3%, P<0.01;42.1% vs 76.0%, P<0.01). β-catenin的表达与nm23H1的表达呈负相关(r = -0.2698, P<0.05).结论:β-catenin和nm23H1的表达与胃癌的分化程度及淋巴结转移有关, 二者在胃癌的侵袭和转移中发挥重要的作用, nm23H1的表达对于Wnt信号通路有一定的抑制作用.     

The expression of HSP70 and LI-caiherin in gastric adenocarcinoma

目的 探讨热休克蛋白70( HSP70)与肝肠钙黏连蛋白(LI-cadherin)在胃腺癌中的表达及其与胃腺癌生物学行为的关系.方法 采用免疫组化SP法检测60例胃腺癌组织中HSP70和LI-cadherin的表达,并分析两种蛋内表达的相关性.结果 HSP70在胃腺癌患者中的表达率为71.67％ (43/60);在低分化胃腺癌患者的表达强度高于高分化型(P＜0.05);伴有淋巴结转移的胃腺癌患者其表达率高于无淋巴结转移者(P＜0.05).LI-cadherin在胃腺癌患者中的表达率为58.33％ (35/60);在高、中型分化胃腺癌的表达高于低分化型,差异有统计学意义(P＜0.05).HSP70与LI-cadherin在胃腺癌中的表达呈正相关,相关系数为(r=0.449,P＜0.05).结论 HSP70与LI-cadherin和胃癌分化程度密相关,且两者在胃腺癌中的表达具有相关性,提示两种蛋白与胃腺癌发展密切相关.     

CD44s mRNA在胃癌组织中的表达及其临床意义

目的探讨CD44s mRNA在胃癌组织中的表达及其临床意义。方法采用核酸原位杂交技术检测66例胃癌（胃癌组）、25例浅表性胃炎（胃炎组）和25例胃上皮不典型增生（增生组）中CD44s mRNA的水平。结果胃炎组无阳性表达;增生组中阳性率为20％;在胃癌组中阳性率为62．12％,胃癌组低分化组织中阳性率明显高于高分化组织（P〈0．05）,有淋巴结转移组阳性率明显高于无淋巴结转移组（P〈0．05）。结论CD44s mRNA表达与胃癌组织分化程度和转移有相关性;CD44s mRNA基因水平可作为判断胃癌病情和预后的指标。     

胃癌淋巴结转移灶与原发灶P-糖蛋白的表达及意义

目的:探讨P-糖蛋白(P-glycoprotein,P—gp)在胃癌淋巴结转移灶与原发灶表达水平的差异及其与胃癌临床病理特征的关系.方法:应用免疫组化的方法检测19例伴有淋巴结转移的胃癌患者的淋巴结转移灶、胃癌原发灶和正常胃黏膜的P—gp表达.结果:淋巴结转移灶P-gp表达的阳性率高于原发灶(84.20％ vs 52.63％,P<0.05);淋巴结转移灶P-gp表达与患者性别、年龄、肿瘤分化程度和浸润深度无关;胃癌原发灶P-gp的表达与胃癌组织分化程度和浸润深度有关(P<0.05),与性别和年龄无关.P-gp表达阳性率在高、中分化者较低分化者高,肿瘤浸润未达浆膜者高于已穿越浆膜者.结论:胃癌淋巴结转移灶的P-gP表达高于原发灶,淋巴结转移灶与原发灶P-gp表达和胃癌临床病理特征的关系不同.     

胃癌组织中β-catenin及Tiam-1 mRNA表达的意义

目的研究胃癌组织中β-catenin和Tiam-1的表达及二者与胃癌分化程度及转移的关系.方法收集胃癌40例及慢性浅表性胃炎(CSG)组织30例,利用逆转录酶链式反应(RTPCR)方法分别检测组织中β-catenin和Tiam-1 mRNA的表达情况.结果在胃癌组织40例中24例有β-catenin mRNA表达(60.0%),β-catenin mRNA的表达与胃癌分化程度及淋巴结转移无关(P＞0.05),在CSG 30例中16例有β-catenin mRNA表达(53.3%),2组比较,差异无统计学意义(x2=0.3111,P＞0.05).在胃癌组织40例中27例有Tiam-1 mRNA的表达(67.5%),在CSG 30例中8例有Tiam-1 mRNA的表达(26.7%),胃癌组织中Tiam-1的阳性率明显高于CSG组(x2=11.4333,P＜0.01),低分化组及淋巴结转移阳性组Tiam-1的阳性率高于高分化组及淋巴结转移阴性组(85.0% vs 50.0%,82.6% vs 47.1%,均P＜0.05).结论β-catenin mRNA表达与胃癌分化程度及转移无关,Tiam-1 mRNA表达与胃癌分化程度及淋巴结转移有关.     

胃癌组织中β-catenin及Tiam-1 mRNA表达的意义

目的:研究胃癌组织中β-catenin和Tiam-1的表达及二者与胃癌分化程度及转移的关系.方法:收集胃癌40例及慢性浅表性胃炎(CSG)组织30例,利用逆转录酶链式反应(RT- PCR)方法分别检测组织中β-catenin和Tiam-1 mRNA的表达情况.结果:在胃癌组织40例中24例有β-catenin mRNA表达(60.0%),β-catenin mRNA的表达与胃癌分化程度及淋巴结转移无关(P>0.05),在CSG 30例中16例有β-catenin mRNA表达(53.3%),2组比较,差异无统计学意义(χ~2= 0.3111,P>0.05).在胃癌组织40例中27例有Tiam-1 mRNA的表达(67.5%),在CSG 30例中8例有Tiam-1 mRNA的表达(26.7%),胃癌组织中Tiam-1的阳性率明显高于CSG组(χ~2= 11.4333,P<0.01),低分化组及淋巴结转移阳性组Tiam-1的阳性率高于高分化组及淋巴结转移阴性组(85.0%vs 50.0%,82.6%vs 47.1%,均P<0.05).结论:β-catenin mRNA表达与胃癌分化程度及转移无关,Tiam-1 mRNA表达与胃癌分化程度及淋巴结转移有关.     

生长抑素的表达与胃黏膜上皮癌变的关系

[目的]探讨生长抑素（ss）在胃黏膜上皮癌发生、发展中的作用及地位，从而为胃癌的诊断、治疗及预后判断提供一个新的途径。[方法]应用免疫组化SABC（Strept Avidin Biotin Complex）法检测78例胃癌组织和20例正常胃黏膜、53例胃黏膜上皮各级癌前病变标本中SS的表达。[结果]SS在正常胃黏膜中阳性表达率为85．0％，癌前病变组织中阳性表达率为43．4％，胃癌组织中阳性表达率为24．3％；高／中分化组和低分化组中的阳性表达率分别为34．2％、13．5％，随分化程度减低呈下降趋势；浸润黏膜层或黏膜下层和浸润肌层或浆膜层两组的阳性表达率分别为64．3％、15．6％，随浸润程度的加深其阳性表达率呈下降趋势；无淋巴结转移组和有淋巴结转移组的阳性表达率分别为38．7％、14．9％；TNMⅠ～Ⅱ期和Ⅲ～Ⅳ期的阳性表达率分别为45．5％、8．9％。以上两组间比较差异均有统计学意义（P〈0．05）。[结论]SS的低表达与胃癌的组织学分级、浸润深度、淋巴结转移及TNM分期密切相关。SS的失表达可能是胃黏膜上皮癌变过程中的重要机制之一。     

p16基因表达与胃癌组织类型的关系

目的：探讨ｐ１６基因的表达与人胃癌组织类型的关系。方法：选取２４例病理确诊的胃癌组织及相应正常胃粘膜组织，用蛋白质免疫印迹（Ｗｅｓｔｅｒｎ ｂｌｏｔ）技术检测ｐ１６基因在两种组织中的表达。结果：２４例胃癌组织中，６例无ｐ１６基因表达的癌组织为低分化腺癌或印戒细胞癌；２例ｐ１６基因表达可疑；分化较高的５例ｐ１６基因表达增多；其们１１例ｐ１６基因的表达同相应正常组织无区别。结论：ｐ１６基因在胃癌组织中     

Amplification and overexpression of the c-erbB-2 protooncogene in human gastric cancer.

The c-erbB-2 protooncogene encodes a possible growth factor receptor. This gene has been studied as to whether it can be regarded as a prognostic indicator in human breast carcinoma. As amplification and overexpression of the gene have been reported in several adenocarcinomas, 24 specimens of human gastric cancers were examined by immunohistochemical staining (24 cases), by Southern blotting (23/24) and by Northern blotting (16/24). Amplification of the gene was detected in two moderately differentiated tubular adenocarcinomas (8.7%), and overexpression of c-erbB-2 mRNA was detected in three moderately differentiated tubular adenocarcinomas (18.8%). By immunohistochemical staining of paraffin-embedded tissues using a polyclonal antibody to c-erbB-2 gene products, the cell membrane was stained positively in three cases of gastric cancers which overexpressed c-erbB-2 mRNA. Peritoneal metastases were found in six gastric cancers, including two moderately differentiated tubular adenocarcinomas in which amplification of c-erbB-2 occurred. These results suggest that amplification and overexpression of c-erbB-2 may be correlated with metastases in differentiated adenocarcinoma of the stomach.     

Association of ezrin expression in intestinal and diffuse gastric carcinoma with clinicopathological parameters and tumor type

AIM： To investigate the correlation between ezrin expression and types of gastric carcinoma and clinicopathological variables.
METHODS： We examined ezrin protein expression in 75 gastric carcinoma （53 intestinal types of adenocarcinoma, 22 diffuse types of carcinoma） tissues by immunohistochemistry. The results were compared with clinicopathological parameters such as tumor type, grade of tumor, clinical stage, presence of metastatic lymph node, and depth of invasion.
RESULTS： Ezrin immunostaining was positive in 43 cases （81.1%） of intestinal type and in 9 （40.9%） cases of diffuse type adenocarcinomas （P 〈 0.001）. In gastric carcinomas, the expression of ezrin protein correlated with the status of H py/ori and survival. There was no correlation between expression of ezrin with TNM stage and histological grade of gastric carcinomas （P 〉 0.05）.
CONCLUSION： The low expression of ezrin implicates the loss of adhesion in diffuse carcinomas. Furthermore, overexpression of ezrin in carcinomas with H pylori infection may be a genuine specific pathway in which Hpylori may cause/initiate gastric carcinoma.     

Expression of thymidylate synthase in human gastric and colorectal adenocarcinomas is upregulated by p16/INK4

BACKGROUND/AIMS: We observed the relationship between the expression of thymidylate synthase protein (pTS) and cell cycle regulators in gastric and colorectal adenocarcinoma tissues. METHODOLOGY: This study included 80 gastric and 50 colorectal adenocarcinomas. Immunohistochemical staining was performed using a polyclonal antibody to recombinant human pTS, and monoclonal antibodies to p53, p21/WAF1CIP1, p16/INK4, cyclin D1 and pRB. Each staining was quantified using computerized image analysis on a CAS 200 system. We selected the mean expression values as the cutoff values to distinguish between high and low expression of these substances. RESULTS: There was no relationship between pTS expression and p21/WAF1CIP1, cyclin D1, or pRB expression in gastric and colorectal carcinomas. In both gastric and colorectal carcinomas, the pTS expression was significantly low in the high p16/INK4 expression subgroup compared with the low p16/INK4 expression subgroup (P < 0.05). Further, the pTS expression was significantly high in the high p53 expression subgroup compared with the low p53 expression subgroup in colorectal adenocarcinomas (P < 0.05). CONCLUSIONS: pTS expression regulation in human gastric and colorectal adenocarcinomas in complex, and upregulated by p16/INK4.     

Expression of pituitary tumor transforming gene in human gastric carcinoma

AIM: Pituitary tumor transforming gene (PTTG1) is overexpressed in a variety of tumors, including carcinomas of the lung, breast, colon, as well as in leukemia, lymphoma and pituitary adenomas. However, there is little information on its expression in gastric carcinoma. We sought to investigate the expression of PTTG1 in gastric carcinoma and to explore the relationship between its expression and clinicopathological factors. METHODS: We studied 75 primary human gastric adenocarcinomas, including 17 mucosal carcinomas, 21 submucosal infiltrative carcinomas, 12 carcinomas invading proprial muscle layers, 6 carcinomas reaching the subserosa, and 19 carcinomas penetrating the serosal surface. Immunohistochemical analysis was performed using paraffin-embedded sections of gastric adenocarcinomas. RESULTS: PTTG1 was expressed heterogeneously in carcinomas. Positive PTTG1 staining was observed in 65.3% of the carcinomas (49 of 75). Its expression did not correlate significantly with either the histological type or the depth of infiltration of the gastric carcinomas. However, a statistical analysis showed significant differences between the primary adenocarcinomas and the associated metastatic lymph nodes. CONCLUSION: The results of this study demonstrate that PTTG1 expression is enhanced in metastatic lymph nodes in comparison to that in primary carcinomas. We suggest that PTTG1 may contribute to lymph node metastases in gastric carcinoma.     

Expression of survivin in human gastric carcinoma and gastric carcinoma model of rats

AIM: To study the expression of survivin, an inhibitor of apoptosis protein, in human gastric carcinomas and gastric carcinoma models of rats.METHODS: With the method of immunohistochemical staining, we studied the expression of survivin in 20 cases of chronic gastritis and 56 cases of gastric carcinomas. We used N-methyI-N‘‘-nitro-N-nitrosoguanidine (MNNG) and high dose sodium-chloride diet to induce rat gastric carcinomas. Survivin expression was studied in glandular stomachs of normal rats, adenocarcinomas and tissues adjacent to the tumor, as well as in rats during the induction period.RESULTS: Survivin was expressed in 27 of 56 (48.2 %) cases of human gastric carcinoma tissues and 1 of 20 (5 %) cases of chronic gastritis. It was found that the expression of survivin had no relation with the elements of age, tumor depth, tumor size, and disease stage, but was significantly related to histological type. The positive rate of survivin expression in cases of intestinal type was significantly higherthan that in cases of diffuse type (P&lt;0.05). In animal experiments, survivin expression in glandular stomachs ofnormal rats, of rats in middle induction period, in adenocarcinomas and tissues adjacent to tumor were 0,40.0 %, 78.3 % and 38.9 %, respectively. Compared with the survivin expression in normal rats, the differences were significant.CONCLUSION: These data imply that survivin plays an important role in the onset of gastric carcinoma and that high survivin expression is an early event of gastric carcinoma.     

肿瘤-睾丸抗原MAGE-1、MAGE-3、SSX-2及NY-ESO-1在胃癌中的表达

目的　检测肿瘤 睾丸 (cancer testis ,CT)抗原MAGE 1、MAGE 3、NY ESO l及SSX 2基因mRNA在胃癌组织中的表达 ,探索其在胃癌免疫治疗中的应用价值。方法　用逆转录聚合酶链反应 (RT PCR)方法对胃癌患者癌组织、相应癌旁组织和对照组织(慢性胃炎和正常胃组织 )中的MAGE 1、MAGE 3、NY ESO 1及SSX 2基因mRNA进行检测 ,结合临床指标进行分析 ,随机选取RT PCR阳性扩增产物进行序列测定。结果　在在检测的 5 0例胃癌组织中 ,MAGE 1、MAGE 3、NY ESO 1及SSX 2基因mRNA阳性率分别是 48% (2 4/5 0 )、42 % % (2 1/5 0 )、11% (6/5 0 )和 8% (4 /5 0 ) ;多个CT抗原基因mRNA在胃癌中同时表达 ,至少表达一种CT抗原者达76% (3 8/5 0 ) ,表达两种或两种以上者为 40 % (2 0 /5 0 ) ,表达三种或三种以上者为 10 % (5 /5 0 ) ,同时表达四种者为 6% (3 /5 0 )。而相应的癌旁组织和对照组织中均未检测到四种目的基因的表达。DNA测序结果表明RT PCR产物确为这四种基因的目的片段。MAGE 1、MAGE 3、NY ESO 1及SSX 2基因的表达与年龄、性别、肿瘤大小、分化程度、浸润深度和淋巴结转移等无显著相关性 (P >0 .0 5 )。结论　CT抗原 (MAGE 1、MAGE 3、NY ESO 1及SSX 2 )基因在胃癌组织中呈高特异表达 ,这使得以这些基因编码的蛋     

Alteration of cyclin D1 in gastric carcinoma and its clinicopathologic significance

AIM: To detect the genetic alteration and abnormal expression of cyclin D1 in gastric carcinoma and investigate its clinicopathologic significance in advanced gastric carcinoma. METHODS: Proteins of cyclin D1 were detected by immunohistochemistry in 42 cases of advanced gastric carcinoma with their follow-up data available, 27 cases of early stage carcinoma, 21 cases of gastric adenoma, 22 cases of hyperplastic polyp and 20 cases of normal mucosa adjacent to adenocarcinomas. Genetic alteration of cyclin D1 was detected by Southern blot and expression of cyclin D1 mRNA was detected by PT-PCR in 42 cases of advanced gastric carcinoma. RESULTS: Cyclin D1 protein was not expressed in normal mucosa, hyperplastic polyp and gastric adenoma, while it was only positively expressed in gastric carcinoma. The expression rate of cyclin D1 protein in early stage gastric carcinoma, advanced gastric carcinoma and lymph node metastasis was 48.1%, 47.4% and 50.0%, respectively. The amplification of cyclin D1 gene was detected in 16.6% of advanced gastric carcinomas. The overexpression of cyclin D1 mRNA was detected in 40.5% of the samples. There was no significant correlation between cyclin D1 protein expression and age, lymph-node metastasis and histological grading in patients with advanced gastric carcinoma (chi2 = 0.038, 0.059, 0.241, P>0.05). Significant correlation was observed between the expression of cyclin D1 protein and the 5-year survival rate (chi2 = 3.92, P<0.05). CONCLUSION: Detection of cyclin D1 protein by immunohistochemistry may be useful in the diagnosis of early gastric carcinomas. Patients with positive expression of cyclin D1 protein tend to have a worse prognosis.     

幽门螺杆菌感染与胃癌组织p16基因变异的关系

目的：探讨幽门螺杆菌（Hp)感染与胃癌组织p16基因变异的关系。方法43例胃癌患者的新鲜癌手术标本、相应的癌旁正常组织及血清标本为本组研究对象,分别采用PCR及银染PCR－SSC癌组织p16基因的纯合性缺失及突变情况;幽门螺杆菌感染状况通过PCR及血清学试验确定。结果（1）43例胃癌中,Hp阳性30例,阳性率为69．77％,其中CagA阳性24例,阳性率为80％。（2）30例Hp阳性胃癌中,有12例发生p16基因变异,发生率为40％;13例Hp阴性胃癌中,4例p16基因发生变异,发生率为30．77％,Hp阳性组与阴性组相比较p16基因变异率差异无显著性（P＞0．05）。（3）30例Hp阳性胃癌中,CagA阳性与阴性组p16基因变异率分别为41．67％（10．24）及33．33％（2／6）,两组变异率比较差异无显著（P＞0．05）。结论Hp及CagA阳性Hp感染与胃癌组织p16基因变异无显著相关性,Hp感染可能不是其改变或必须因素。     

Significance of the expression of p27Kip1 in esophageal squamous cell carcinomas

Recent observations have demonstrated that the reduced expression of p27Kip1 (p27) is correlated with progression and poor prognosis of breast, colon, and gastric carcinomas. These observations led us to examine the expression of p27 and cyclin D1 and E protein in six esophageal carcinoma cell lines and 81 esophageal carcinoma tissues by Western blot analysis and immunohistochemistry. The expression levels of cyclin D1 and p27 were correlated clearly in esophageal carcinoma cell lines by Western blot analysis. Immunohistochemical analysis revealed that the high-grade expression of p27 protein was detected in 61% of esophageal carcinomas, and it was correlated with tumor invasion, lymph node metastasis, and poor patient prognosis. This observation was different from the results reported in other organs. Cell cycle regulation is a very complicated process. Homeostatic feedback mechanisms against the overexpression of cyclin D1 may exist in esophageal carcinomas, and there can be organ-specific regulations in the progression of carcinomas.