HER-2在胃癌原发灶和转移淋巴结中的表达

目的:探讨HER-2蛋白表达与胃癌临床病理特征的关系以及HER-2蛋白表达与基因扩增的关系,并探讨原发灶与转移灶中HER-2基因扩增及表达的异质性.方法:用免疫组织化学(immunohistoc hemistry,IHC)、荧光原位杂交(fluorescence in-situ hybridization,FISH)检测180例胃癌原发灶及112例转移淋巴结中HER-2的表达情况及基因状态,将检测结果进行比较,并与临床病理特征进行统计学分析.结果:180例胃癌原发灶IHC染色0、1+、2+及3+的例数分别为139(77.2%)、16(8.9%)、15(8.3%)及10(5.6%),即HER-2蛋白阳性表达率为13.9%;112例淋巴结转移灶IHC染色0、1+、2+及3+的例数分别为80(71.5%)、9(8.0%)、14(12.5%)及9(8.0%),即HER-2蛋白阳性表达率为20.5%,两者无显著性差异(P>0.05);原发灶和淋巴结转移灶FISH与IHC阳性符合率分别为84.0%、82.6%;112例淋巴结转移灶与其对应原发灶相比,有6例IHC和/或FISH结果不一致,其中3例发生了蛋白表达的阳性转变,2例发生了基因状态的阳性转变,未发现阴性转变;HER-2的表达与TNM分期、Lauren分型、有无淋巴结转移、浸润深度、分化程度有关(P<0.05).结论:HER-2蛋白过表达与基因扩增有较好的一致性;HER-2过表达与胃癌的浸润和转移有关;HER-2基因扩增及表达在胃癌原发灶与转移灶中具有异质性;若原发灶HER-2阴性,应进一步检测转移灶.     

进展期胃癌HSP90α、CD44v6表达与其临床生物学行为关系的研究

目的:探讨HSP90α、CD44v6在进展期胃癌中的表达特点及其生物学行为,为进展期胃癌的临床治疗提供理论依据.方法:对9 3例进展期胃癌及其5 6例淋巴结转移癌中HSP90α、CD44v6的表达,应用免疫组化方法进行检测.结果:HSP90α在胃癌及淋巴结转移癌中的阳性率分别为54.84%(51/93)、66.07%(37/56).HSP90α在胃癌中表达分别与癌细胞浸润深度、淋巴结转移及TNM分期有关(P＜0.0.5);CD44v6在胃癌及淋巴结转移癌中的阳性率分别为50.54%(47/93)、73.21%(41/56),二者之间的差异显著(P＜0.01).CD44v6在胃癌中的表达分别与癌细胞分化程度、浸润深度、淋巴结转移及TNM分期有关(P＜0.05).结论:进展期胃癌中HSP90α、CD44v6阳性表达与其临床生物学行为尤其是淋巴结转移密切相关,患者可能预后较差,应采取积极的综合治疗措施.     

进展期胃癌HSP900α、CD44v6表达与其临床生物学行为关系的研究

目的:探讨HSP90α、CD44v6在进展期胃癌中的表达特点及其生物学行为,为进展期胃癌的临床治疗提供理论依据. 方法: 对93例进展期胃癌及其56例淋巴结转移癌中HSP90α、CD44v6的表达,应用免疫组化方法进行检测. 结果:HSP90α在胃癌及淋巴结转移癌中的阳性率分别为54.84% (51/93)、66.07%(37/56).HSP90α在胃癌中表达分别与癌细胞浸润深度、淋巴结转移及TNM分期有关(P<0.05); CD44v6在胃癌及淋巴结转移癌中的阳性率分别为50.54% (47/93)、73.21%(41/56),二者之间的差异显著(P<0.01). CD44v6在胃癌中的表达分别与癌细胞分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05). 结论:进展期胃癌中HSP90α、CD44v6阳性表达与其临床生物学行为尤其是淋巴结转移密切相关,患者可能预后较差,应采取积极的综合治疗措施.     

应用组织芯片研究凋亡抑制基因Survivin在胃癌中的表达

目的　检测Survivin和CD44v6在胃癌中的表达,以探讨二者在胃癌中表达的相关性及其与预后的关系。方法　利用组织芯片技术构建胃癌组织芯片,应用免疫组织化学S P法检测Survivin和CD44v6蛋白在胃癌中的表达。结果　胃癌中Survivin及CD44v6的总表达率分别为 58 6% (58 /99)和 35 4% (35 /99)。Survivin在早期胃癌中的表达显著高于进展期胃癌 (P<0 05 ),与胃癌的其它临床病理特征无相关性。CD44v6阳性表达与胃癌生长方式(P<0 001)、浸润深度 (P<0 05 )及淋巴结转移 (P<0 001 )密切相关。Sur vivin和CD44v6在胃癌中的表达无相关性(r=-0 065,P>0 05)。Survivin与胃癌患者的生存率无显著相关,而CD44v6表达阳性组 5年生存率(16 13% )显著低于CD44v6表达阴性组 5年生存率(60 67% ) (P<0 001 )。结论　Survivin和CD44v6在胃癌中均有过量表达。Survivin可能参与胃癌发生、发展的早期过程;而CD44v6阳性表达与胃癌的浸润和转移密切相关,同时可以提示胃癌的不良预后。     

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.     

VEGF、CD44v6及p27在胃癌组织中的表达及其临床意义

目的探讨血管内皮细胞生长因子(VEGF)、CD44v6及p27在胃癌中的表达并判断其与胃癌发生的关系。方法应用S-P法,对63例胃癌组织及相应的癌旁组织、28例正常胃组织进行VEGF、CD44v6及p27蛋白检测,并研究其与病理分期的相关性。结果胃癌组织中p27阳性表达率显著下降,VEGF、CD44v6阳性表达率显著升高(P0.05);胃癌组织中,分化程度低、侵及浆膜、有淋巴结转移及TNM分期高者,p27阳性表达率显著下降,VEGF、CD44v6阳性表达率显著升高(P0.05);胃癌中VEGF表达与p27表达呈负相关(r=-0.614 P0.05);与CD44v6表达呈正相关(r=0.614 P0.05);p27的表达与CD44v6表达呈负相关(r=-0.745 P0.05)。结论 VEGF、CD44v6及p27表达与胃癌发生发展、浸润、转移有关,预示这三种蛋白的表达可能与胃癌的治疗和预后具有显著关系,为临床治疗胃癌提供新的思路。     

CD44v6在胃癌胃镜标本和术后标本中的表达及与胃癌生物学行为的关系

目的:研究CD44v6在胃癌胃镜标本和术后标本中的表达,并分析其与胃癌生物学行为的关系.方法:随机选取辽宁医学院附属第二医院普通外科2004-2009年收治的有详细病例资料的胃癌患者50例,应用免疫组织化学方法检测胃镜标本和术后标本胃组织中CD44v6的表达.结果:CD44v6在胃癌胃镜标本、术后标本和转移淋巴结中的表达率分别为60.00%、64.00%、80.77%.显著高于胃良性病变(P＜0.01);CD44v6在肠型胃癌中的表达率显著高于弥漫型胃癌(75.86% vs 47.62%,P＜0.05).胃癌胃镜和术后标本中CD44v6的表达与胃癌浸润深度,TNM分期和淋巴结转移均有关(P＜0.05).CD44v6在胃癌胃镜标本和术后标本中的总体表达率无显著性差异(P＞0.05);相同临床病理参数,CD44v6在胃癌胃镜标本和术后标本中的表达率无显著性差异(P＞0.05).结论:CD44v6可作为术前预测胃癌的发生、病期进展和转移潜能的辅助生物学指标之一.     

整合素α2β1及CD44v4在胃癌组织中的表达及意义

目的讨论整合素α2β1和CD44v4在胃癌组织中的表达及意义。方法采用免疫组化SP法检测85例胃癌标本和50例癌旁正常胃组织中整合素α2β1和CD44v4的表达情况,分析二者的表达与胃癌生物学行为以及它们之间的相关性。结果①整合素α2β1与CD44v4在胃癌标本中的阳性表达率均高于癌旁正常组织(P<0.05)。②整合素α2β1和CD44v4在胃癌中的表达与胃癌的分化程度、TNM分期、淋巴结转移和浸润深度有关(P<0.05)。③整合素α2β1和CD44v4在胃癌中的表达呈正相关(r=0.517,P<0.05)。结论整合素α2β1和CD44v4在胃癌中高表达且在胃癌的浸润、转移过程中起正协同作用,并且与胃癌的分化程度、TNM分期、淋巴结转移和浸润深度密切相关,与患者的年龄、性别以及病理组织学类型无关。     

VEGF和CD44v6过表达与乳腺癌浸润转移的关系

目的检测血管内皮生长因子(VEGF)和转移相关黏附分子44v6(CD44v6)在乳腺癌中的表达情况,探讨两者与淋巴结转移的关系。方法采用免疫组化SP法检测92例乳腺浸润性癌中VEGF、CD44v6的表达情况。结果 VEGF在正常乳腺组织和乳腺癌中的阳性表达率分别为6.7%(3/45)和90.2%(83/92),且VEGF在淋巴结转移组中的阳性表达率(53/55)明显高于无淋巴结转移组(P<0.05)。CD44v6在正常乳腺组织及乳腺癌中的阳性表达率分别为8.9%(4/45)和85.9%(79/92),而且CD44v6在淋巴结转移组中的阳性表达率(51/55)明显高于无淋巴结转移组(P<0.05)。VEGF和CD44v6表达呈正相关关系(r=0.497,P<0.05)。结论 VEGF、CD44v6在乳腺癌组织中高表达,且均与淋巴结转移有关(P<0.05),两者可能在乳腺癌的远处转移中起协同作用。     

一氧化氮合酶和微血管生成与胃癌发展的关系

目的　研究诱导型一氧化氮合酶 (iNOS)在人胃癌组织中的表达及其与胃癌微血管形成、淋巴结转移及临床分期的关系。方法　采用免疫组化S P法检测 50例原发性胃癌组织、癌周组织及 2 0例正常胃黏膜组织中iNOS的表达 ,同时检测微血管密度 (MVD) ,以抗CD3 4标记血管内皮细胞 ,并分析其与肿瘤行为之间的关系。结果　 50例胃癌组织中iNOS阳性表达率为 70 .0 % ,MVD均值为 2 2 .0± 9 .8,显著高于癌周组织 (16.2 % ,6.1± 3 .4)和正常胃组织 (15.0 % ,5.5± 2 .6;P <0 .0 1)。按TNM分期 ,Ⅳ期胃癌组织iNOS阳性表达率为 93 .8% ,MVD为 42 .3± 3 .7,两者显著高于Ⅰ、Ⅱ、Ⅲ期 ,差异有显著性 (P <0 .0 1)。有淋巴结转移组iNOS的阳性表达率为 84.6% ,MVD均值为 2 7.4± 6.5;无淋巴结转移组iNOS阳性表达率为 54.2 % ,MVD均值为 15.3± 4.7,两组差异有显著性 (P <0 .0 5)。iNOS阳性表达组及高MVD值 (≥ 2 2 .0 )组的 3年生存率均显著低于iNOS阴性表达组及低MVD值 (<2 2 .0 )组 ,差异有显著性 (P <0 .0 5)。结论　胃癌组织中iNOS高阳性表达 ,随着iNOS阳性表达的增强 ,MVD值也增加 ,两者呈正相关。iNOS的表达及MVD与胃癌TNM分期、淋巴结转移及预后有密切关系。iNOS的表达及MVD值可作为判断胃癌预后的重要指标     

CD44在肺癌中表达的临床研究

目的观察标准型白细胞分化抗原（ＣＤ４４ｓ）及变异型白细胞分化抗原（ＣＤ４４ｖ６）在肺癌中的表达情况及同肺癌淋巴结转移的关系。方法以ＳＰ法对９６例原发性肺癌及１２例转移淋巴结行免疫组化研究。结果在小细胞肺癌（ＳＣＬＣ）中，未见ＣＤ４４表达；而在非小细胞肺癌（ＮＳＣＬＣ）中，鳞癌（ＳＣＣ）的ＣＤ４４表达明显高于腺癌（ＡＤＣ）（Ｐ＜０．０１）；在１２例转移淋巴结中，１０例（８３％）表达ＣＤ４４ｖ６阳性；同未发生淋巴结转移的原发性肺癌（５１％）相比，发生转移的原发性肺癌中ＣＤ４４ｖ６表达明显增多（９１％，χ２＝１４．９２，Ｐ＜０．０１）；ＣＤ４４ｓ及ＣＤ４４ｖ６表达同肺癌分化程度无关；按ＴＮＭ分期，Ⅲ＋Ⅳ期中ＣＤ４４ｖ６表达显著高于Ⅰ＋Ⅱ期肺癌（χ２＝６．０５，Ｐ＜０．０５）。结论ＣＤ４４大部分表达于ＮＳＣＬＣ中，且主要在ＳＣＣ中；ＣＤ４４ｖ６阳性可能预示ＮＳＣＬＣ发生淋巴结转移的倾向，并可能对肺癌临床分期起到一定作用     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.     

Expression of c-erbB-2 and c-met proteins in gastric adenoma and adenocarcinoma]

BACKGROUND/AIMS: The aim of this study was to investigate the immunohistochemical overexpression of c-erbB-2 and c-met proteins according to the histopathological parameters such as grade of dysplasia, histological type, depth of invasion, lymph node metastasis, and TNM stage in gastric adenoma and gastric adenocarcinoma. METHODS: Immunohistochemical staining using monoclonal c-erbB-2 and c-met antibodies was performed on paraffin embedded specimens in 43 adenomas and 44 adenocarcinomas. RESULTS: The expression rate of c-erbB-2 was higher in adenomas (91%) than adenocarcinomas (30%). The expression rate of c-met was higher in adenocarcinomas (77%) than adenomas (49%). In adenoma, the expression rate of c-met was higher in high grade dysplasia (94%) than in low grade dysplasia (22%). In adenocarcinoma, c-met expression was significantly related with lymph node metastasis. CONCLUSIONS: c-erbB-2 would be involved in the development of relatively early stage gastric carcinogenesis. c-erbB-2 is related with histologic type and c-met with lymph node metastasis in gastric carcinomas. Although meaning for the expression of these proteins in gastric carcinomas would be different, these proteins may play as important oncogenes in gastric carcinogenesis.     

Differential gene and protein expression in primary gastric carcinomas and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis

OBJECTIVE: To gain insight into the molecular events of lymph node metastasis of human gastric carcinoma. METHODS: The gene expression profile of five matched primary gastric carcinomas and their lymph node metastases was analyzed by complementary DNA (cDNA) microarray. Differential genes were identified in the metastatic and corresponding primary tumor pairs. Among the differentially expressed genes, carbonic anhydrase II (CAII) and insulin-like growth factor binding protein 4 (IGFBP 4) genes were detected by RT-PCR. CTTN protein expression was examined by tissue microarray. RESULTS: There was a high expression (over twofold) of 44 genes and a low expression (under twofold) of 32 genes in lymph node metastasis compared with primary gastric carcinoma, respectively. CAII mRNA was downregulated and IGFBP 4 mRNA was upregulated in paired lymph node metastases of gastric carcinomas. The overexpression of CTTN protein was related to the lymph node metastasis and the clinical stage of gastric carcinomas. CONCLUSION: This study showed that there is a low expression of genes relative to growth signal and immune response in lymph node metastases, and a high expression of genes relative to growth factor, cell cycle, cell motility and adhesion in lymph node metastases compared with primary gastric carcinomas. The expression of CTTN was related to the invasion and metastasis of gastric cancer.     

Expression of proliferating cell nuclear antigen and CD44 variant exon 6 in primary tumors and corresponding lymph node metastases of colorectal carcinoma with Dukes＇＇ stage C or D

AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ stage C or D.METHODS: Formalin fixed and paraffin embedded materials of primary tumors and corresponding lymph node metastases resected from 56 patients with Dukes′ stage C or D of colorectal carcinoma were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44variant exon 6 (CD44v6).RESULTS: Thirty-one of 56 patients (55.4 %) expressed PCNA in the primary sites and 36 of 56 patients (64.3 %)expressed PCNA in the metastatic lymph nodes. A significant relation in PCNA expression was observed between the primary site and the metastatic lymph node (0.010＜P＜0.025).Forty-one of 56 patients (73.2 %) expressed CD44v6 in the primary site and 39 of 56 patients (69.6 %) expressed CD44v6 in the metastatic lymph node. There was also an significant relationship of CD44v6 between the primary site and the metastatic lymph node (0.005＜P＜0.010). No difference was observed between expression of CD44v6 and PCNA in the primary site (0.250＜P＜0.500).CONCLUSION: This study partially demonstrates that tumor cells in metastatic lymph node of colorectal carcinoma still possess cell proliferation activity and metastatic ability of tumor cells in primary site. There may be no association between cell proliferation activity and metastatic ability in colorectal carcinoma.     

CD44v6基因变异体在胃癌中的表达及其与淋巴结转移的关系

探讨胃癌中ＣＤ_（４４）ｖ６基因变异体的表达及其与淋巴结转移的关系。方法：采用免疫组织化学技术,对７５例手术切除胃癌标本中的ＣＤ_（４４）ｖ６基因变异表达产物进行检测。结果： ７５例胃癌标本中,５６例ＣＤ_（４４）ｖ６基因变异体呈阳性表达,占７４．７％;而５５例有淋巴结转移的标本中４６例呈阳性表达（８３．６％）,２０例无淋巴结转移的标本中１０例呈阳性表达（５０％）,差异有显著性（Ｐ＜０．００１）;正常胃粘膜不表达ＣＤ_（４４）ｖ６基因变异体。这一结果提示,ＣＤ_（４４）ｖ６基因变异体的表达与胃癌的淋巴结转移关系密切。结论：含ｖ６外显子的ＣＤ_（４４）变异表达产物可作为预测胃癌淋巴结转移潜能较可靠的分子标记物。     

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.