HER-2/neu基因在原发性肝癌中的表达及意义

目的 探讨原癌基因HER-2／neu在原发性肝癌(PHC)、肝硬化及正常肝组织中的表达状况及意义。探讨应用单克隆抗体Herceptin治疗肝癌的可能性。方法 采用免疫组织化学的方法检测肝癌、肝硬化及正常肝组织中HER-2／neu蛋白的表达。结果 HER-2／neu在(PHC)、肝硬化及正常肝组织中的表达率分别为37．5％(15／40)、10％(1／10)和无表达；其表达与PHC的类型无关，与肿瘤包膜侵犯、病理分级及肿瘤转移有关；而与肿瘤大小、AFP水平及肝硬化无关。结论 HER-2／neu基因在PHC的侵袭性生长转移和发展中可能具有一定的促进作用，可作为PHC独立的预后因子；可考虑应用Herceptin对PHC进行生物学靶向治疗。     

Her 2/neu和MMP2在胰腺癌中的表达及其意义

笔者应用免疫组织化学法检测Her 2 /neu和MMP2基因在 3 4例胰腺癌、5例胰腺囊腺瘤、5例胰腺囊肿和 2例正常胰腺组织中的表达水平。结果示胰腺癌中Her 2 /neu和MMP2表达明显高于胰腺正常组织和良性病变 (P <0 .0 5)。Her 2 /neu的表达在有淋巴结转移的胰腺癌中明显低于无淋巴结转移的胰腺癌 (P <0 .0 5) ;随TNM分期增高 ,其表达阳性率显著降低。MMP2表达在肿瘤直径大于 4.5cm及有淋巴结转移的胰腺癌中均明显高于肿瘤直径小于 4.5cm及无淋巴结转移者 (P <0 .0 5) ;随TNM分期增高 ,其表达阳性率也增高。MMP2在预后不良组中表达水平较生存组高 ,但差异无显著性 (P >0 .0 5)。提示Her 2 /neu和MMP2过度表达可能与胰腺癌的发生发展有关 ;Her 2 /neu可能在胰腺癌发生转移之前发挥作用 ,而MMP2与胰腺癌的侵袭、转移密切相关。检测二者表达水平对指导临床治疗和评估预后可能有较重要价值。     

HER-2/neu过表达与雄激素非依赖性前列腺癌Gleason分级和临床分期的相关性研究

目的:检测HER-2/neu基因在雄激素依赖与雄激素非依赖性前列腺癌(PCa)组织中的表达情况,推测这一基因在雄激素非依赖性PCa发生中的意义。方法:收集30例雄激素依赖性PCa标本(雄激素依赖组)和24例激素非依赖性PCa标本(雄激素非依赖组),采用免疫组化方法检测HER-2/neu基因的蛋白表达,对照临床分期、Gleason分级进行分析。结果:HER-2/neu在雄激素依赖性PCa标本中的阳性表达率为10%,在雄激素非依赖性PCa的表达为33%;Gleason分级≤7分病例中HER-2/neu阳性表达率显著低于Gleason分级>7分病例组(14.29%vs26.92%,P<0.01);临床分期>T2病例中HER-2/neu阳性表达率显著高于≤T2病例组(34.62%vs7.14%,P<0.01)。结论:HER-2/neu在雄激素非依赖性PCa标本中阳性表达率高,而且随临床分期和Gleason分级的升高其阳性表达率升高。     

尿液脱落细胞HER-2/neu基因扩增/17号染色体多倍体在尿路上皮癌诊治中的意义

我们采用荧光原位杂交法(FISH)检测了尿液脱落细胞HER 2 /neu基因扩增与17号染色体的数量变化,探讨了其在尿路上皮癌诊治中的意义。一、材料和方法1.选取2 0 0 0年1月～2 0 0 2年8月间经治的尿路上皮癌10 9例,其中男70例,女2 9例。肾盂输尿管癌13例,膀胱癌96例,手术标本进行病理检查证实诊断。5例良性尿路疾病作为正常对照。取患者自行排尿的尿液2 0～10 0ml用于FISH和尿液细胞学检查。2 .FISH检测:采用双色DNA探针(Vysis公司) ,分别与染色体17q11.2 q12(LSIHER 2 /neuSpectrumOrange )和17p11.1 q11.1(CEP17SpectrumGreen)…     

乳腺癌中HER-2蛋白表达及基因扩增检测的比较研究

Objective To compare HER-2 state in breast cancer tissue deteced by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) and analyze their correlation. Methods HER-2/neu protein expression and gene amplification were detected by FISH and IHC in 56 newly-diagnosed cases of female breast cancer from July 2008 to July 2009. Results Of the 56 patients, HER-2 protein expression (-), (+), (++), (+++) was 9 cases (16.1%), 29 cases (51.8%), 11 cases (19.6%) and 7cases (12.5%) respectively; 26 cases (46.4%) had HER-2 gene amplification while 30 cases (53.6%) didnt have. Type of HER-2 gene amplification was mainly HER-2(++) and HER-2(+++), and according gene amplification rate was 72 7% and 100%. HER-2 (+) gene amplification rate was 37.9 %(11cases) and no gene amplification was found in HER-2(-) tissue. The HER-2 positive rate using two methods had significant difference(χ2=19.778,P<0.01). HER-2(-) and HER-2(+++) had good consistency with the FISH results(Kappa=0.969),but HER-2(+) and HER-2(+ +) were poorly consistent with the FISH results(Kappa=0.271). Conclusions IHC is the preliminary screening method for detection of HER-2 expression. HER-2(-) and HER-2(+++) have good consistency with the gene amplification, and can guide clinical treatment. Some patients with HER-2(+) and HER-2(++) have HER-2 gene amplification. FISH is needed for targeted therapy.     

HER2/neu在胃癌中的作用研究进展

HER2/neu参与了多种肿瘤的发生、发展过程。它通过信号转导途径与多种相关基因协同参与肿瘤细胞的增殖、凋亡、浸润与侵袭作用,出现过表达及高扩增,并可能影响患者的预后。在胃癌治疗中,针对HER2/neu的靶向治疗取得了重要进展。     

用DAKO HercepTest检测肝细胞癌HER-2／neu蛋白的表达

目的研究肝细胞癌(HCC)中HER-2／neu蛋白的表达及其临床病理意义，探讨应用trastuzumab治疗HCC的可能性。方法应用DAKO HereepTest抗体，EnVision二步法对868例外科切除病理诊断为HEE标本的HER-2／neu蛋白的表达情况进行观察，并对其与临床病理特征的关系进行统计学分析。结果868例HCC，有62例(7．14％)出现HER-2／neu蛋白表达，其中41例大于10％的区域有阳性表达，胞膜显色不连续(1 )；20例大于10％的区域有阳性表达，胞膜显色连续，呈局灶强阳性或弥漫中等强度(2 )；1例出现70％的瘤细胞弥漫强阳性胞膜阳性(3 )。其余806例无HER-2／neu染色，瘤周肝组织均阴性。HER-2／neu蛋白表达与HCC的临床病理特征如HBV感染、血清AFP水平、肿瘤大小、组织学分级、胞膜是否完整、有无肝内转移和肝硬化等无明显关系。结论仅少数HCC(4．84％，42／868)过度表达HER-2／neu蛋白，且与各种临床病理指标无明显相关性，表明其不是HCC的一个重要预后指标，仅个别病例有可能应用抗HER-2／neu单克隆抗体trastuzumab治疗。     

Her-2/neu在老年乳腺癌中的表达

目的：分析65岁以上老年乳腺癌的Her-2/neu状态。方法：对65岁以上老年乳腺癌161例进行免疫组化检测。结果：主要病理类型为浸润性导管癌（76.4%）,有脉管瘤栓的19例,40.3%的患者合并其他疾病。免疫组化结果显示HER-2（＋＋＋）占17.4%,HER-2的表达在可手术组与不可手术组有统计学差异（P〈0.05）。结论：老年乳腺癌HER-2状态与分期呈负相关,提示老年乳腺癌患者的预后可能更好。     

CC3/TIP30蛋白在乳腺癌中的表达及其与HER-2/neu基因的相关性研究

目的 分析CC3/TIP30蛋白在乳腺癌中的表达及临床意义,并探讨CC3/TIP30与HER-2/neu的mRNA相关性.方法 采用免疫组化EnVision二步法检测2004年1月至2005年1月手术治疗并病理证实的112例乳腺癌标本中CC3/TIP30、HER-2/neu蛋白的表达,分析其表达与临床病理特征及预后的相关性,同时应用化学合成靶向敲除CC3/TIP30 mRNA的siRNA,并转染SK-BR-3细胞株48 h后,应用real-time PCR法测定CC3/TIP30、HER-2/neu基因mRNA的表达水平.结果 免疫组化显示CC3/TIP30蛋白在乳腺癌组织中表达与TNM分期、淋巴结转移、HER-2和分子分型相关(P=0.048、0.019、0.027、0.011),而与患者年龄、肿瘤大小,以及雌激素受体和孕激素受体表达状态无关.实时定量PCR结果示CC3/TIP30 siRNA转染导致CC3/TIP30 mRNA的表达下降,同时伴随着HER-2/neu基因mRNA水平的下降,差异有统计学意义(F=56.797,F=165.101;P均=0.000).分子分型为HER-2阳性型的乳腺癌患者中CC3/TIP30蛋白表达阳性、阴性组患者5年总生存率差异有统计学意义(X2=10.732,P=0.001).结论 CC3/TIP30蛋白表达缺失与乳腺癌的发生、发展有关,提示乳腺癌患者早期发生转移复发可能,可作为HER-2阳性型乳腺癌亚组分型的指标之一.     

Expression of the cerbB-2 (HER-2/neu) oncoprotein in prostatic adenocarcinoma

We report a 62 years old kidney transplant (KT) patient who was diagnosed of localized prostatic cancer (PC) after 6 years of the implant. Transrectal prostatic High Intensity Focused Ultrasound (HIFU) was applied. Results have been satisfactory, achieving pathologic and biochemical success. The discharge was completed at 24 hs, the morbidity was minimal. We have not found any reference in the literature on the appliance of HIFU in PC KT patients. We think that HIFU may represent a good alternative for these patients.     

抑癌基因DPC4在大肠癌组织中的表达及其临床意义

目的　探讨大肠癌组织中DPC4的表达及其与大肠癌淋巴结转移、临床分期、分化程度等的关系。方法　大肠癌切除手术标本 48例 ,用逆转录 聚合酶链反应 (RT PCR )检测DPC4mRNA相对表达量 ;免疫组织化学方法和Westemblot分析检测DPC4蛋白表达情况。结果　半定量RT PCR显示癌旁正常组织中都有DPC4mRNA表达 ,部分癌组织中表达缺失 ;癌组织为 0 .15±0 .0 6,癌旁组织为 0 .5 3± 0 .15 ,差异有显著性 (P <0 .0 0 1)。其表达程度与肿瘤大小、细胞分化程度、淋巴结的转移及临床分期有关 ;与患者性别、年龄、肿瘤部位无关。免疫组织化学结果为 :癌旁组织大多数表达在 ～ ,癌组织大多表达成 -～ ,癌组织表达程度显著低于癌旁正常组织。DPC4蛋白表达程度与肿瘤大小、细胞分化、临床分期及淋巴结转移有关。Westernblot分析结果为 :48例大肠癌组织中有 10例表达呈阴性。结论　DPC4的表达与大肠癌密切相关 ,将来有可能作为大肠癌诊断和治疗过程中一种具有重要价值的生物学标记物。     

HER-2/neu Expression in Primary Breast Cancer With Sentinel Lymph Node Metastasis

Background Amplification of the protein product of the HER-2/neu oncogene in primary breast cancer specimens is associated with an adverse prognosis. We hypothesized that overexpression of HER-2/neu would predict metastases to the sentinel lymph nodes (SLNs). Methods A retrospective review of a prospective nonrandomized evaluation of 1055 clinically node-negative breast cancer patients undergoing 1063 SLN biopsies was performed. HER-2/neu analysis was performed by immunohistochemistry and, in selected cases, by fluorescence in situ hybridization. Clinical, demographic, surgical, radiological, and pathologic data were analyzed by using generalized estimating equations logistic regression models. Results Two hundred thirty-two (23.6%) of 985 operations in which the SLN was found at operation resulted in positive nodes. In a multivariate analysis, size (P < .0001) and HER-2/neu overexpression (P = .026) were independent predictors of SLN metastasis. Conclusions Size is a known predictor of SLN metastasis in the modern SLN era, as it was in the pre-SLN eras. HER-2/neu was found to be significantly predictive of SLN metastasis in our study. We anticipate a future when even the relatively minor procedure of SLN biopsy might be avoided with the predictive information gained from studying the pathology and molecular markers of primary breast cancers.     

CD133在结肠直肠癌中的表达及临床相关性

目的:探讨CD133在结肠直肠癌病人肿瘤组织中的表达及其与临床病理指标的关系。方法:采用免疫组化法检测83例结肠直肠癌病人的肿瘤组织与癌旁正常组织中CD133的表达,分析其与临床病理指标的相关性。结果:与癌旁正常组织相比,结肠直肠癌组织表达较高水平的CD133。CD133的高表达与肿瘤病理低分化、淋巴结转移等因素密切相关(P0.05)。结论:CD133在结肠直肠癌病人的肿瘤组织中表达显著升高,并与肿瘤的低分化、淋巴结转移密切相关。     

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目的　研究HER 2 /neu(c erbB 2 )在结、直肠恶性肿瘤中的表达及其与肿瘤分期的相关性。方法　收集 2 0 0 2年 1月至 2 0 0 3年 5月治疗的 2 8例结、直肠恶性肿瘤的临床资料。按Dukes分期标准进行分期 ,其中A、B期共 17例 (17/2 8,6 0 7% ) ,C、D期 11例 (11/2 8,39 3% )。采用HER 2单克隆抗体试剂套盒行免疫组织化学染色 ,并以染色细胞数目的多少及染色程度为分级标准 ,认为 2 以上 (含 2 )为过表达 (报告为 ～ 的 ,记为阴性 )。结果　该蛋白在A、B期肿瘤中的过表达率为 11 8% (2 /17) ;C、D期肿瘤中过表达率为 5 4 5 % (6 /11)。该蛋白的过表达率在有转移和无转移的病例之间差异有显著意义 (P <0 0 5 )。结论　虽然在结、直肠恶性肿瘤病例中HER 2 /neu的过表达率不高 ,但仍提示HER 2 /neu过表达程度与肿瘤的进展或侵袭性生物学行为相关。     

Prognostic value of HER-2/neu and p53 expression in node-positive breast cancer. HER-2/neu effect on adjuvant tamoxifen treatment

HER-2/neu and p53 expression, conventional clinical and pathologic prognostic factors, were evaluated in a retrospective series of 283 node-positive breast cancer patients. Overexpression was determined by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53 expression was related to lymph node involvement (P=0.03), necrosis (P=0.036), absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome. HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05) and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis showed that the number of involved axillary nodes (P<0.00001), age (P=0.004), grade (P=0.04), and PR (P=0.04) were independent predictors for OS. ER-positive patients treated with adjuvant tamoxifen had shorter DFS and OS when they were HER-2/neu positive.     

Expression of cyclooxygenase-2 in breast carcinogenesis and its relation to HER-2/neu and p53 protein expression in invasive ductal carcinoma

The purpose of this study was to evaluate cyclooxygenase-2 (COX-2) expression in the successive steps of breast carcinogenesis and to determine its correlation with HER-2/neu and p53 expression in invasive ductal carcinomas of the breast. Immunohistochemical staining with anti-COX-2 antibody was performed in normal breast tissue, usual hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Expression of COX-2 in invasive ductal carcinoma was correlated with immunohistochemical expression of HER-2/neu and p53 protein. COX-2 expression was found to be progressively elevated along the continuum from normal breast tissue to invasive ductal carcinoma (P<0.001). COX-2 expression significantly correlated with p53 and HER-2/neu protein expression (P<0.05 and P<0.001). On multivariate analysis, only TNM stage and elevated COX-2 expression correlated with survival. Our results suggest that COX-2 may be involved in the carcinogenesis of the breast and may be an independent prognostic indicator in patients with invasive ductal carcinoma. HER-2/neu and p53 are likely to be involved in the regulation of COX-2 expression in invasive ductal carcinomas of the breast.