胃癌组织nm23和c-erbB_2癌基因蛋白表达与根治术后再发癌的关系

目的探讨ｎｍ２３和ｃｅｒｂＢ２癌基因蛋白表达与胃癌根治术后再发癌发生的关系．方法采用免疫组化ＳＰ法检测６４例胃癌中ｎｍ２３和ｃｅｒｂＢ２的表达，并结合内镜及随访资料进行分析．结果胃癌ｎｍ２３低表达率及ｃｅｒｂＢ２阳性率在淋巴结转移组及术后３ａ内有再发癌组明显增高，ｎｍ２３低表达率及ｃｅｒｂＢ２阳性率：有淋巴结转移组为６８９％（３１／４５）和４２２％（１９／４５）；无淋巴结转移组为３６８％（７／１９）和１５８％（３／１９）；术后３ａ内再发癌组为８１０％（１７／２１）和５２４％（１１／２１）；术后３ａ以上无再发癌组为４８８％（２１／４３）和２２６％（１１／４３）（Ｐ＜００５）．而且ｎｍ２３低表达与肿瘤浸润程度有关，浸至浆膜及周围脏器组ｎｍ２３低表达率为７８６％（２２／２８）；浸至粘膜及粘膜下组者为４００％（６／１５）（Ｐ＜００５）．结论胃癌ｎｍ２３低表达和ｃｅｒｂＢ２阳性表达者具有较强的浸润、转移能力，且术后易发生再发癌，二者的表达变化对判断胃癌术后再发癌的发生及预后有重要意义     

胃粘膜肠化中幽门螺杆菌感染与PCNA,c-erbB-2的表达

目的研究肠化胃粘膜幽门螺杆菌（Ｈｐ）阳性率与ＰＣＮＡ,ｃｅｒｂＢ２表达率之间关系,以探讨Ｈｐ感染在胃肠化发生、发展中作用．方法经病理检查证实的慢性胃炎伴肠化１１６例,对照组非溃疡性消化不良．应用改良ＷａｒｔｈｉｎＳｔａｒｙ法检测Ｈｐ,免疫酶组化ＳＰ法检测ＰＣＮＡ,ｃｅｒｂＢ２的表达,比较Ｈｐ阳性组和阴性组间ＰＣＮＡ,ｃｅｒｂＢ２的阳性表达率．结果胃粘膜肠化者Ｈｐ感染率增高（５８６％ｖｓ１８８％,χ２＝１０７９,Ｐ＜００１）,肠化胃上皮内少见Ｈｐ粘附,Ｈｐ阳性组ＰＣＮＡ,ｃｅｒｂＢ２表达高于阴性组（４８／６８ｖｓ１２／４８,χ２＝９０５,Ｐ＜００５;３６／７４ｖｓ２／４２,χ２＝１３２８,Ｐ＜００１）．结论Ｈｐ感染促进胃粘膜肠化,并使肠化胃粘膜细胞增殖迅速而启动恶性变,故Ｈｐ感染可能促进胃癌的形成．     

C-myc,Bcl-2与胃癌生物学行为和细胞凋亡

目的探讨癌基因Ｂｃｌ２，Ｃｍｙｃ的表达变化与胃癌生物学行为和细胞凋亡的关系．方法采用免疫组化ＬＳＡＢ法，检测６０例原发性胃癌组织（男３８例，女２２例，年龄３７岁～７５岁）癌基因Ｂｃｌ２，Ｃｍｙｃ蛋白的表达变化；在普通光学显微镜下对受检组织的ＨＥ片进行形态学测量和凋亡细胞计数．结果受检组织６０例中，Ｃｍｙｃ阳性表达３７例（６２％），其表达与分化程度和临床分期呈显著性相关，且Ｃｍｙｃ阳性组织细胞凋亡指数（０７±０３）明显高于阴性组织（０３±０２）；所检标本中，Ｂｃｌ２阳性表达率为６８％（４１／６０），其中高分化胃癌的阳性表达率明显高于低分化胃癌（３２％ｖｓ９％）（Ｐ＜００５），阳性Ｂｃｌ２组织与阴性Ｂｃｌ２组织比较，前者凋亡指数明显低于后者（０４±０３ｖｓ０９±０５）（Ｐ＜００５）．结论Ｃｍｙｃ与Ｂｃｌ２基因的异常表达是胃癌生物学行为的重要影响因素，二者在胃癌形成过程中均起着一定的作用，并对细胞增生与凋亡有重要调节作用．     

胃粘膜癌变过程中幽门螺杆菌感染与p53,c-erbB-2基因表达的研究

目的探讨胃粘膜癌变过程中幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,Ｈｐ）感染与ｐ５３,ｃｅｒｂＢ２基因表达的关系．方法浅表性胃炎１６例,肠上皮化生２２例,异型增生１４例,早期胃癌１８例及进展期胃癌４０例作为研究对象．用ＷａｒｔｈｉｎＳｔａｒｙ银染色法检测Ｈｐ,用免疫组化Ｓｐ法检测ｐ５３和ｃｅｒｂＢ２的基因表达产物．结果Ｈｐ,ｐ５３,ｃｅｒｂＢ２在浅表性胃炎的检出率各为５００％,００％,００％;在肠上皮化生的检出率各为５９１％,２２７％,１３６％;在异型增生的检出率各为８５７％,６４３％,２８６％;在早期胃癌的检出率各为１６７％,３３３％,１１１％;在进展期胃癌的检出率各为５０％,５２５％,５５０％;在癌旁粘膜的Ｈｐ检出率为８６７％;在癌前病变中,Ｈｐ阳性组的ｐ５３,ｃｅｒｂＢ２表达率均高于Ｈｐ阴性组．结论Ｈｐ感染参与了胃癌前病变的发生与发展;Ｈｐ感染可引起野生型ｐ５３基因失活和ｃｅｒｂＢ２基因激活,从而导致胃粘膜的癌变．     

p53 C-myc和P-gp蛋白在胃癌细胞中表达

目的研究胃癌组织中ｐ５３和Ｃｍｙｃ的表达与多药耐药性（ＭＤＲ）的关系．方法应用ＬＳＡＢ免疫组织化学方法研究６７例（男４１例，女２６例，平均年龄４６±１５８岁）胃癌标本中ｐ５３，Ｃｍｙｃ和Ｐｇｐ的表达．结果本组胃癌中ｐ５３阳性３２例（４７８％），Ｃｍｙｃ阳性３７例（５５２％），Ｐｇｐ阳性３９例（５８２％）．淋巴结转移阳性胃癌ｐ５３阳性率（５６９％）和Ｃｍｙｃ阳性率（６４７％）显著高于淋巴结转移阴性的胃癌（Ｐ＜００５）．ｐ５３的异常表达与ｍｄｒ１基因表达呈显著正相关（ｒ＝０６３，Ｐ＜００５），而Ｃｍｙｃ和ｍｄｒ１的表达无明显相关．结论ｐ５３异常表达可增加ｍｄｒ１基因的表达，从而使胃癌细胞获得ＭＤＲ表型     

差别PCR技术检测胃癌C一erbB-2癌基因扩增的临床意义

目的探讨胃癌Ｃ－ｅｒｂＢ－２癌基因扩增的临床意义。方法应用差别ＰＣＲ技术检测Ｃ－ｅｒｂＢ－２在８３例胃癌及１０１个转移淋巴结扩增情况。结果２８．９％（２４／８３）的胃癌存在该基因扩增，进展期胃癌及伴淋巴结转移者扩增阳性率增高（Ｐ＜０．０５及Ｐ＜０．０１）；转移淋巴结扩增阳性率明显高于胄癌原发灶（Ｐ＜０．０５）。早期胃癌及高中分化胃癌伴Ｃ－ｅｒｂＢ－２扩增者５年生存率低于不扩增者（Ｐ＜０．０５）。用Ｓｏｕｔｈｅｒｎｂｌｏｔ分子杂交及免疫组化ＡＢＣ法检测原胃癌样本基因扩增及过度表达，扩增及过度表达率分别为１５．７％及１８．１％，均明显低于上述扩增阳性率。结论差别ＰＣＲ技术检测Ｃ－ｅｒｂＢ－２扩增是一种快速方便、可靠、独立的方法，对胃癌预后及转移潜力是一种良好的判断指标。     

人胃癌组织中金属蛋白酶类基因的过度表达

目的探讨组织金属蛋白酶家族成员在人胃癌组织中的表达．方法应用免疫组织化学（ＳＰ法）和原位杂交（ｃＤＮＡｍＲＮＡ）技术对４１例人胃癌１７例癌旁组织中的金属蛋白酶ＭＭＰ２，ＭＭＰ９及ＭＴＭＭＰ基因表达进行检测．结果ＭＭＰ２及ＭＴＭＭＰ蛋白在胃癌及癌旁组织阳性率分别为７３１％（３０／４１），６５８％（２７／４１）和２２５％（４／１７），４１１％（７／１７）．胃癌及癌旁组织ＭＭＰ２，ＭＭＰ９及ＭＭＰＭＴｍＲＮＡ阳性率分别为７０７％（２９／４１），５１２％（２１／４１），５６０％（２３／４１）和２３５％（４／１７），２３５％（４／１７），３５２％（６／１７）．一致性检验显示基因的免疫组化和原位杂交检验结果的关系密切（Ｐ＜００５）．结论ＭＭＰｓ基因的过度表达参与了胃癌的发生发展过程，ＭＭＰｓ的免疫组化是检测胃癌组织侵袭、转移倾向的可靠方法．     

nm23-H1蛋白在胃癌中的表达

目的ｎｍ２３Ｈ１基因被认为是肿瘤转移抑制基因．本研究旨在探讨此基因的蛋白表达与胃癌转移之间的关系．方法使用抗人ｎｍ２３Ｈ１单克隆抗体，采用抗生蛋白链菌素—生物素标记的免疫组织化学染色方法，检测ｎｍ２３Ｈ１蛋白在５２例手术切除的胃癌及其淋巴结转移癌中的表达．结果ｎｍ２３Ｈ１蛋白表达与性别、年龄及胃癌的组织学类型无关．原发癌中ｎｍ２３Ｈ１表达阳性率（３６５％）明显高于转移癌（１２５％，Ｐ＜００１）．无淋巴结转移者及浆膜累及者，ｎｍ２３Ｈ１表达的阳性率（６６７％，６００％）明显高于有淋巴结转移者及浆膜累及者（２７５％，２７０％，Ｐ＜００５）．结论本研究结果表明ｎｍ２３Ｈ１蛋白在抑制胃癌浸润及淋巴结转移中发挥重要作用．     

胃粘膜癌前病变P21和P53蛋白的表达

目的检测胃粘膜肠化生和异型增生病变部位Ｐ２１和Ｐ５３蛋白表达与胃癌发生的关系．方法内窥镜及病理学证实为胃粘膜肠化生者４４例，男２６例，女１８例，平均年龄４７５岁．异型增生者１４例，男９例，女５例，平均年龄６４５岁．粘液组化将肠化生分型，免疫组化测定Ｐ２１及Ｐ５３蛋白表达．结果Ⅱｂ型肠化生Ｐ２１及Ｐ５３蛋白阳性率分别为７００％和３００％，均显著高于Ⅰｂ型肠化生（２５８％和６４％，Ｐ＜００１）．异型增生Ｐ２１及Ｐ５３阳性率为４２８％和２８５％，高于肠化组３４％和１１８％．Ⅱｂ型肠化异型增生Ｐ２１和Ｐ５３阳性率为６２５％和３７５％，也高于Ⅰｂ型肠化异型增生组１６６％和１６６％．结论分泌非中性粘液的Ⅱｂ型肠化异型增生带有更多与胃癌相同的生物学性状，可能与胃癌的发生关系密切．     

胃粘膜异型增生形态与p53,Bcl-2和c-erbB-2表达的关系

目的了解胃粘膜异型增生形态与ｐ５３，ｂｃｌ２和ｃｅｒｂＢ２表达的关系．方法胃粘膜炎症性增生４５例，异型增生４４例和胃腺癌３０例，胃粘膜活检标本进行组织形态观察，并采用ＳＰ免疫组化法，观察ｐ５３，ｂｃｌ２和ｃｅｒｂＢ２基因表达．结果异型增生病灶，小者仅有单个腺管，多者达１０余个腺管，多数３个～５个腺管．异型腺管有不同程度的扩张，为圆形或不规则形，腺上皮细胞单层或复层排列．核大小不等，染色质粗，核形态不一，为圆形、椭圆形或不规则形，可见核仁或核分裂．异型增生的腺管与周围的腺管分界清，这种现象称之为胃粘膜腺管区域性异型增生．异型增生腺管ｐ５３，ｂｃｌ２和ｃｅｒｂＢ２基因蛋白表达分别为９１％，７２７％和３８６％．结论胃粘膜腺管区域性异型增生与胃腺癌关系密切．     

Expression of the c-erbB-2 proto-oncogene product in gastric carcinoma and precancerous lesions

AIM: To study the relationship between the expression of the c-erbB-2 proto-oncogene product with gastric mucosal carcinogenesis and the behavior of gastric carcinoma.METHODS: Specimens from nine normal gastric mucosa, 23 gastric mucosal dysplasia (10 slight, six moderate, seven severe), 18 early gastric carcinoma, and 30 advanced gastric carcinoma were marked with P₁₈₅ monoclonal antibody using the immunohistochemical peroxidase-avidin-biotin complex method. The relation between P₁₈₅ expression with histological type, size, and lymph node metastasis of gastric carcinoma were analyzed.RESULTS: Normal gastric mucosa was negative for P₁₈₅; Only a few cells in the neck region of the mucosal glands were very weakly positive. Relatively high positive rates were found in the slight, moderate, and severe dysplasia specimens (50%, 83.3%, and 85.7%, respectively). A 22.2% and 56.7% P₁₈₅-positive rate was found in early gastric carcinoma and in advanced gastric carcinoma, respectively. Statistically, the P₁₈₅-positive rates in severe dysplasia and advanced gastric carcinoma were significantly higher than that in early gastric carcinoma (P < 0.05). The P₁₈₅-positive rate in the group with lymph node metastasis was significantly higher than that of the group without lymph node metastasis (59.3% vs 23.8%, P < 0.05), but P₁₈₅ expression was not related to histological type and size of gastric carcinoma.CONCLUSION: The c-erbB-2 proto-oncogene might participate in gastric mucosal proliferation, repair, and carcinogenesis, and gastric carcinoma with P₁₈₅ expression might have a stronger potential of infiltration and metastasis.     

胃癌及癌前病变组织中CD44v6表达的意义

目的探讨CD44v6基因表达与胃癌发生及胃癌生物学行为的关系.方法应用抗CD44v6蛋白的单克隆抗体,采用免疫组化ABC方法对正常胃粘膜(n=10)、各级胃粘膜异型增生(轻度n=16,中度n=12,重度n=14)、早期胃癌(n=16)及进展期胃癌(n=52)进行研究,并与胃癌类型、大小、有无淋巴结转移等作了比较分析.结果正常胃粘膜CD44v6为阴性,随着胃粘膜病变的进展,CD44v6蛋白的表达率逐渐升高,至进展期胃癌,表达率达到顶峰.轻、中、重度异型增生表达率分别为12%,33%,43%;早期胃癌及进展期胃癌的表达率分别为44%和73%.各级异型增生表达率之间的差异无显著性,而进展期胃癌表达率显著高于早期胃癌(P＜0.05),淋巴结转移组的表达率显著高于淋巴结未转移组(82%vs56%,P＜0.05),肠型胃癌的表达率高于弥漫型胃癌(78%vs56%,P＜0.05),CD44v6蛋白的表达与胃癌肿块大小无相关性.结论胃粘膜重度异型增生在CD44v6基因表达上已具有明显的潜在恶性趋势,CD44v6基因表达阳性的胃癌具有更强的浸润及淋巴结转移的能力.     

慢性糜烂性胃炎与胃癌的免疫组织化学比较研究——P~(21ras)、 P~(53)、PCNA和CEA表达的观察

本研究对31例慢性糜烂性胃炎粘膜活检组织及14例手术切除的胃癌组织的P21ras、P53蛋白、细胞核增殖抗原（PCNA）、癌胚抗原（CEA）的表达采用LSAB免疫组织化学标记。结果发现P21ras在慢性糜烂性胃炎粘膜上皮和胃癌肿瘤细胞中表达阳性率分别为67.7％和65.0％（P>0.05）;P53表达阳性率分别为0和21.4％（0.010.05）;CEA表达阳性率分别为29.0％和78.6％（P<0.01）。慢性糜烂性胃炎较高的P21ras表达和较高的细胞增生活性（PCNA表达）,提示其有一定的转化趋势。慢性糜烂性胃炎粘膜上皮的CEA表达可能提示其为今后发展成肠型胃癌的前驱病变。     

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     

Expression, deleton and mutation of p16 gene in human gastric cancer

AIM To investigate the relationship between the expression of p16 gene and the gastric carcinogenesis,depth of invasion and lymph node metastases, and to evaluate the deletion and mutation of exon 2 in p16 gene in gastric carcinoma. METHODS The expression of P16 protein was examined by streptavidin-peroxidase conjugated method (S-P); the deletion and mutation of p16 gene were respectively examined by polymerase chain reaction (PCR) and polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) in gastric carcinoma. RESULTS Expression of P16 protein was detected in 96.25% (77/80) of the normal gastric mucosa, in 92.00% (45/50) of the dysplastic gastric mucosa and in 47.54% (58/122) of the gastric carcinoma. The positive rate of P16 protein expression in gastric carcinoma was significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P＜0.05). The positive rate of P16 protein expression in mucoid carcinoma 10.00% (1/ 10) was significantly lower than that in poorly differentiated carcinoma 51.22% ( 21/ 41 ),undifferentiated carcinoma 57.69% (15/26) and signet ring cell carcinoma 62.50% (10/ 16) (P＜0.05). The positive rate of p16 protein in 30 cases paired primary and lymph node metastatic gastric carcinoma: There was 46.67% (14/30) in primary gastric carcinoma, 16.67% (5/30) in lymph node metastatic gastric carcinoma. The positive rate of lymph node metastatic carcinoma was significantly lower than that of primary carcinoma (P＜0.05). There was of p16 gene mutation in exon 2, but 5 cases displayed deletion of p16 gene in exon 2 in the 25 primary gastric carcinomas. CONCLUSIONS The expression loss of P16 protein related to the gastric carcinogenesis, gastric carcinoma histopathological subtypes and lymph metastasis. The mutation of p16 gene in exon 2 may not be involved in gastric carcinogenesis. But the deletion of p16 gene in exon 2 may be involved in gastric carcinogenesis.     

胃癌、胃黏膜不典型增生和胃炎组织中p185和p21蛋白的表达及其临床意义

目的研究胃癌、胃黏膜不典型增生和胃炎组织中c-erbB-2和ras癌基因产物p185和p21蛋白的表达,以探讨p185和p21蛋白在胃癌发生、发展过程中的作用。方法采用免疫组化S-P法检测39例胃癌组织、24例胃黏膜不典型增生组织和33例胃炎组织p185和p21蛋白的表达。结果p185蛋白在慢性胃炎、轻度胃黏膜不典型增生组织中不表达;在中、重度胃黏膜不典型增生组织中的表达率分别为11.8%和66.7%,差异有显著性(P<0.05),表达程度明显增强(P<0.05);在高、中、低分化胃癌组织中的表达率分别为77.8%、50.0%和29.2%,差异有显著性(P<0.05),高分化胃癌组织中p185蛋白的表达程度明显高于中、低分化胃癌组(P<0.05)。p21蛋白在胃黏膜不典型增生及胃癌组织中的表达率和表达程度较慢性胃炎组明显增高,差异有显著性(P<0.01);在轻、中、重度胃黏膜不典型增生组织中的表达率分别为25.0%、82.4%和100.0%,差异有显著性(P<0.05),表达程度明显增强(P<0.05);在高、中、低分化胃癌组织中的表达率分别为44.4%、66.7%和95.8%,差异有显著性(P<0.01),表达程度明显增强(P<0.05)。p185和p21蛋白在胃癌组织中的表达呈负相关(r=-0.450,P<0.01)。结论c-erbB-2和ras癌基因产物p185和p21蛋白在胃癌致病机制中起重要作用,p21蛋白作用于胃癌发生的早期阶段,p185蛋白可能作用于胃癌发生的较晚期。     

Expression, deletion [was deleton] and mutation of p16 gene in human gastric cancer

AIM: To investigate the relationship between the expression of p16 gene and the gastric carcinogenesis, depth of invasion and lymph node metastases, and to evaluate the deletion and mutation of exon 2 in p16 gene in gastric carcinoma. METHODS: The expression of p16 protein was examined by streptavidin-peroxidase conjugated method (S-P);the deletion and mutation of p16 gene were respectively examined by polymerase chain reaction (PCR) and polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) in gastric carcinoma. RESULTS: Expression of p16 protein was detected in 96.25% (77/80) of the normal gastric mucosa, in 92.00% (45/50) of the dysplastic gastric mucosa and in 47.54% (58/122) of the gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma was significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P < 0.05). The positive rate of p16 protein expression in mucoid carcinoma 10.00% (1/10) was significantly lower than that in poorly differentiated carcinoma 51.22% (21/41), undifferentiated carcinoma 57.69% (15/26) and signet ring cell carcinoma 62.50% (10/16) (P < 0.05). The positive rate of p16 protein in 30 cases paired primary and lymph node metastatic gastric carcinoma: There was 46.67% (14/30) in primary gastric carcinoma, 16.67% (5/30) in lymph node metastatic gastric carcinoma. The positive rate of lymph node metastatic carcinoma was significantly lower than that of primary carcinoma (P < 0.05). There was of p16 gene mutation in exon 2, but 5 cases displayed deletion of p16 gene in exon 2 in the 25 primary gastric carcinomas. CONCLUSIONS: The expression loss of p16 protein related to the gastric carcinogenesis, gastric carcinoma histopathological subtypes and lymph metastasis. The mutation of p16 gene in exon 2 may not be involved in gastric carcinogenesis. But the deletion of p16 gene in exon 2 may be involved in gastric carcinogenesis.     

单克隆抗体SC3A在胃癌及癌前病变的表达意义

目的研究单克隆抗体ＳＣ３Ａ在胃癌及癌前病变的表达意义．方法应用免疫组化ＡＢＣ法及粘液组化染色检测１０１例胃良恶性病变组织中ＳＣ３Ａ的表达．结果胃癌７１例中ＳＣ３Ａ阳性５７例（８０３％），但与癌组织类型、分化程度、转移及术后生存率无明显关系．ＳＣ３Ａ阳性率在酸性粘液（＋）组胃癌明显高于酸性粘液（－）组（９０２％对２００％，Ｐ＜００１），硫酸粘液（＋）组胃癌明显高于硫酸粘液（－）组（９１３％对６００％，Ｐ＜００１）．而且癌旁肠化硫酸粘液阳性率明显较良性病变伴肠化高（８８９％对３５３％，Ｐ＜００１）；硫酸粘液（＋）组肠化ＳＣ３Ａ阳性率明显高于硫酸粘液（－）组（６０９％对３１３％，Ｐ＜００５）．结论单克隆抗体ＳＣ３Ａ的表达对胃癌诊断及组织发生探讨有一定意义．