上皮性卵巢癌组织中EGFR、EGFR mRNA、LRP和LRP mRNA表达水平及其临床意义

目的 探讨上皮性卵巢癌卵巢组织中表皮生长因子受体(EGFR)、卵巢组织中表皮生长因子受体信使RNA(EGFR mRNA)、肺耐药蛋白(LRP)和肺耐药蛋白信使RNA(LRP mRNA)表达水平及临床意义.方法 选取经过手术治疗且确诊为上皮性卵巢癌的98例患者进行研究.另选择取同期体检为健康人群的30例女性作为对照组.通...     

EGFR及其信号通路分子在上皮性卵巢癌中的表达及其临床意义

目的:探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)、丝氨酸/苏氨酸蛋白激酶ERK及细胞外信号调节激酶AKT mRNA在上皮性卵巢癌的表达及其临床意义。方法:选取2008年12月至2010年4月青岛大学医学院附属医院经病理证实的上皮性卵巢癌61例,RT-PCR检测上皮性卵巢癌、良性卵巢肿瘤和正常卵巢组织中EGFR、AKT、ERK mRNA的表达,并结合上皮性卵巢癌临床病理资料分析其临床意义。结果:上皮性卵巢癌组织中EGFR、ERK和AKT mRNA的阳性表达率高于正常卵巢及良性卵巢肿瘤组织(78.7%vs14.3%、31.3%,80.3%vs35.7%、35.7%,90.2%vs21.4%、25.0%;P<0.01)。EGFR、AKT mRNA的表达与肿瘤临床分期、细胞分化和淋巴结转移有关(P<0.05),与组织学类型和年龄无关(P>0.05);ERK mRNA的表达与细胞分化程度相关(P<0.05)。AKT mRNA和ERK mRNA的表达具有相关性(r=0.048,P<0.05)。结论:EGFR、AKT、ERK的表达与上皮性卵巢癌的发生、发展相关。     

LRP与c-erbB-2在上皮性卵巢癌中的表达及临床意义

目的探讨肺耐药蛋白(lungresistanceprotein,LRP)与c-erbB-2在上皮性卵巢癌中的表达及其临床意义。方法采用免疫组织化学SP法检测108例上皮性卵巢癌组织和10例正常卵巢组织中LRP和c-erbB-2的表达,并进行相关的临床病理参数分析。结果LRP和c-erbB-2在上皮性卵巢癌中的阳性表达率分别为70.4%和64.8%,而正常卵巢组织中均未见表达,两者表达差异均有显著性(P<0.05)。上皮性卵巢癌组织中LRP的表达与上皮性卵巢癌组织学类型、临床分期、病理分级、患者年龄、残留病灶等临床病理参数无关。c-erbB-2的表达与组织学类型、临床分期、患者年龄和残留病灶无关,与病理分级有关(P<0.05)。LRP表达阳性的卵巢癌患者对化疗的反应率(44.7%)明显低于LRP表达阴性者(93.7%)(P<0.05);c-erbB-2表达阳性的卵巢癌患者对化疗的反应率(42.8%)明显低于c-erbB-2表达阴性者(89.4%)(P<0.05)。结论LRP和c-erbB-2在上皮性卵巢癌中有较恒定的表达,且阳性表达预示化疗反应率低,可能成为预测卵巢癌化疗耐药的指标。     

MMP-2在上皮性卵巢癌中的表达及临床意义

目的:探讨MMP-2在上皮性卵巢癌中的表达及临床意义.方法:15例正常卵巢组织、15例良性上皮性卵巢肿瘤组织, 89例上皮性卵巢癌组织标本,用免疫组化法检测MMP-2蛋白表达.结果:正常卵巢组织及良性卵巢肿瘤组织中,MMP-2蛋白不表达或低表达.上皮性卵巢癌中,MMP-2表达水平明显升高,高表达率为50.6%.MMP-2高表达与肿瘤晚期、瘤细胞的低分化、肿瘤转移有显著的相关性(P<0.05).结论:上皮性卵巢癌组织中,MMP-2蛋白表达上调.MMP-2蛋白在上皮性卵巢癌的生长和转移过程中发挥重要作用,有可能作为判断卵巢癌预后的指标.     

肌成束蛋白-1在上皮性卵巢癌组织中的表达及临床意义

摘 要：［目的］ 研究肌成束蛋白-1（FSCN1）在上皮性卵巢癌组织中的表达及与预后相关性。［方法］ 选取2010年1月至2014年12月我院收治的120例卵巢肿瘤患者作为研究对象,包括80例上皮性卵巢癌,40例卵巢良性上皮肿瘤。采用免疫组化检测FSCN1在癌组织、癌旁组织和良性组织中的表达水平。免疫组化检测上皮间质转化（epithelial mesenchymal transformation,EMT）关键蛋白波形蛋白（vimentin）和E钙黏蛋白（E-cadherin）在卵巢癌组织中的表达水平。［结果］ FSCN1在卵巢癌组织中的高表达率（67.5%,54/80）明显高于癌旁组织（28.8%,21/73）和良性卵巢组织（12.5%,5/40） (χ2=41.02,P<0.001)。FSCN1表达水平与临床病理分期、淋巴结转移具有相关性（P=0.023;P=0.026）,FSCN1表达水平与Vimentin表达水平呈正相关（P=0.007）,而与E-cadherin表达水平呈负相关（P=0.006）。FSCN1高表达水平患者总生存率（27.5%）明显低于FSCN1低表达水平的患者（52.3%）（P=0.007）,FSCN1高表达是上皮性卵巢癌患者不良预后的独立风险因素（P=0.011）。［结论］ FSCN1在上皮性卵巢癌中高表达,且与卵巢癌的恶性程度密切和EMT相关,对于预测卵巢癌的预后具有一定的价值。     

上皮性卵巢癌组织中KDF1表达及临床意义

目的 探讨角化细胞分化因子1(KDF1)在上皮性卵巢癌(EOC)组织中表达与辅助化疗耐药和预后的关系。方法 收集癌症基因组图谱(TCGA)数据库中的数据(n=379)分析EOC中KDF1 mRNA的表达模式和预后价值。收集大同市第五人民医院病理科135例福尔马林固定石蜡包埋组织,包括111例EOC组织,12例卵巢良性肿瘤组织和12例卵巢畸胎瘤组织。采用免疫组化染色法检测组织KDF1表达。患者化疗结束后,采用实体肿瘤疗效评价标准1.1版评估辅助化疗反应,完全缓解(CR)和部分缓解(PR)纳入敏感亚组,疾病稳定(SD)和疾病进展(PD)纳入耐药亚组。结果 通过对TCGA数据库中的卵巢癌数据进行差异表达分析,发现KDF1在卵巢癌患者中呈高表达(P<0.001),并与卵巢癌患者较低的总体生存率(OS)相关。在临床验证队列中,EOC组织中KDF1蛋白表达明显高于畸胎瘤组织和卵巢良性肿瘤组织(P<0.001)。根据KDF1免疫染色强度评分中位值,将EOC患者分为KDF1低表达组(<7.67分)和高表达组(≥7.67分)。辅助化疗耐药亚组组织KDF1蛋白评分显著高于敏感亚组(P&l...     

Ezrin蛋白在卵巢上皮性癌中的表达及临床意义

目的探讨Ezrin蛋白在卵巢上皮性癌组织中的表达及与其临床病理因素的关系及临床意义。方法应用免疫组化sP法,检测85例卵巢上皮性癌术后组织和20例良性上皮性肿瘤组织中Ezrin蛋白的表达情况。结果卵巢上皮性癌组织中Ezrin蛋白表达率低于卵巢良性肿瘤,差别有统计学意义（50．14％VS89．76％,P〈0．001）;晚期卵巢上皮性癌（FIGOⅢ～Ⅳ）中Ezrin蛋白表达率低于早期卵巢癌（FIGOⅠ～Ⅱ）（38．9％VS74．2％,P〈0．001）;Ezrin蛋白低表达或缺失与细胞分级（P=0．036）、组织学类型（P=0．024）和残留肿瘤大小有关（P=0．012）,与患者年龄及肿瘤大小无关（P〉0．05）;良性肿瘤组织中Ezrin蛋白主要分布在细胞膜上,上皮性癌组织中主要以胞质染色为主,少部分分布在胞膜;单因素分析显示：Ezrin低表达或缺失患者疾病无进展生存时间、总生存率明显缩短（P〈0．001,P=0．01）。多因素COX回归模型显示：Ezrin蛋白低表达或缺失是无进展生存时间、总生存率的独立危险因素。结论Ezrin蛋白与卵巢癌的浸润及转移密切相关,是卵巢癌独立的不良预后因素。     

TM4SF1 蛋白在上皮性卵巢癌组织中的表达及其临床意义

目的 探讨跨膜四超家族成员1（transmembrane 4 super family 1,TM4SF1）蛋白在人卵巢组织中的表达及其与上皮性卵巢癌临床病理因素的关系。方法 采用免疫组化SP法检测16例正常卵巢上皮组织、23例上皮性卵巢良性肿瘤组织及55例上皮性卵巢癌癌组织中TM4SF1蛋白的表达情况,分析其与上皮性卵巢癌临床病理因素及预后的关系。结果 ①TM4SF1蛋白在上皮性卵巢癌癌组织中的阳性表达率（90.90%）高于上皮性卵巢良性肿瘤组织（65.22%）及正常卵巢上皮组织（25.00%）的阳性表达率,差异有统计学意义（P〈0.05）。②TM4SF1蛋白在正常卵巢上皮细胞中的表达主要位于上皮细胞的细胞膜和细胞膜近基底膜处及细胞质中,在卵巢良性肿瘤组织中的表达主要集中在肿瘤细胞的细胞膜近基底膜处及细胞膜其他部位,而在卵巢癌细胞中则主要分布于癌细胞的细胞质中。③Ⅲ～Ⅳ期卵巢癌患者TM4SF1蛋白的阳性表达率高于Ⅰ～Ⅱ期患者,中低分化癌患者TM4SF1蛋白的阳性表达率高于高分化癌患者（P〈0.05）。④TM4SF1蛋白的阳性表达率与组织学类型、腹水量的多少无明显相关（P〉0.05）,而与FIGO分期及组织学分级明显相关（P〈0.05）。⑤Cox比例风险回归模型多因素分析显示TM4SF1蛋白在卵巢癌癌组织中的阳性表达不是影响患者生存的独立预后因素。结论 TM4SF1蛋白在上皮性卵巢癌癌组织中呈高表达,可能与卵巢癌的发生、发展相关。     

miR-506和FGF2在上皮性卵巢癌中的表达及临床意义

目的:检测上皮性卵巢癌组织微小RNA-506（miR-506）和成纤维细胞生长因子2（FGF2）表达情况,并探究其临床意义。方法:选取2011年3月至2012年12月本院收治的上皮性卵巢癌患者56例,选择同期因子宫良性病变在平煤神马医疗集团总医院接受全子宫双附件切除的患者56例（对照组）;采用实时定量PCR（qRT-PCR）法检测miR-506表达水平,采用免疫组化法检测FGF2表达水平,采用全自动化学发光免疫分析仪检测血清糖类抗原125（CA125）水平。结果:上皮性卵巢癌组织miR-506表达水平较正常卵巢组织显著降低（P＜0.05）,FGF2表达量显著高于正常卵巢组织（P＜0.05）,FGF2蛋白表达阳性率较正常卵巢组织显著升高;上皮性卵巢癌组织中miR-506、FGF2表达与患者临床分期、有无淋巴结转移、血清CA125水平有关（P＜0.05）,与患者年龄、组织学类型无关（P＞0.05）;miR-506高表达上皮性卵巢癌患者术后5年总生存率显著高于低表达者（P＜0.05）,FGF2高表达上皮性卵巢癌患者术后5年总生存率显著低于低表达患者（P＜0.05）;Pearson检验结果显示,卵巢癌肿瘤组织miR-506与FGF2表达水平负相关。结论:miR-506在上皮性卵巢癌组织中低表达,FGF2高表达,与患者临床分期、淋巴结转移、血清CA125水平有关,可能作为上皮性卵巢癌患者病情监测及预后的生物指标。     

Rho和ROCK蛋白在上皮性卵巢癌中的表达及临床意义

目的探讨上皮性卵巢癌Rho和ROCK蛋白的表达及其与上皮性卵巢癌进展之间的关系。方法应用Western blot方法,观察了66例上皮性卵巢癌和22例正常卵巢组织Rho和ROCK蛋白的表达,并分析Rho/ROCK蛋白表达与生存期的关系。结果RhoA、C和ROCK蛋白在卵巢癌组织中表达增加,且在伴有肿瘤转移的淋巴组织中表达高于没有肿瘤转移的淋巴组织(P<0.05)。RhoA、C和ROCK间的表达呈正相关(P<0.05),RhoA、C和ROCK的表达与肿瘤分化、淋巴转移和短综合生存期相关(P<0.05)。多变量分析显示,只有RhoC是影响生存的独立因素(P<0.05)。RhoA和C是影响综合生存期的因素(P<0.05)。结论在上皮性卵巢癌中,RhoA、C和ROCK蛋白高表达,Rho/ROCK通路可能参与了上皮性卵巢癌的进展。     

Targeting epidermal growth factor receptor in lung cancer

Among the most promising agents in clinical development to treat non-small-cell lung cancer (NSCLC) are the epidermal growth factor receptor (EGFR) targeting agents. A series of recent studies have demonstrated the activity of anti-EGFR targeted therapies for NSCLC. In advanced NSCLC that is refractory to chemotherapy, antitumor responses have been reported with EGFR tyrosine kinase inhibitors (ZD1839 and OSI-774). The role of ZD1839 and OSI-774 as possible additions to standard chemotherapy in the first-line setting has also been evaluated, and the studies conducted to date should respond to the question of whether these compounds could provide a survival benefit. Other areas of research involve looking at the role of EGFR tyrosine kinase inhibitors in the neoadjuvant treatment of stage III NSCLC and the planning of chemoprevention studies. These exciting results and plans are further complemented by an emerging number of compounds in clinical development, including both monoclonal antibodies (ie, IMC-C225) and other tyrosine kinase inhibitors, directed at the EGFR.     

生长抑素受体亚型与 EGFR在非小细胞肺癌中的表达及其临床意义

目的:探讨联合应用凋亡素(apoptin)基因、新城疫病毒(newcastle disease virus,NDV)血凝素-神经氨酸酶(he-magglutinin-neuramidinase,HN)基因及人白介素18(hIL-18)基因体外对人结肠癌细胞HCT-116的抑制效应。方法:重组质粒pIRApoptinHNIL18通过脂质体介导法体外转染人结肠癌细胞HCT-116,通过Western blotting和RT-PCR检测外源基因表达;采用AO/EB染色法检测pIRApoptinHNIL18对人结肠癌细胞HCT-116抑制作用;利用流式细胞术分析pIRApoptinHNIL18对人结肠癌细胞HCT-116线粒体膜电位(mitochondrial transmembrane potential,△Ψ)和活性氧(reactive oxygen species,ROS)水平;采用3,5-二羟基甲苯法测定唾液酸含量。结果:pIRApoptinHNIL18转染人结肠癌细胞HCT-116后,外源基因能够有效表达;肿瘤细胞生长受到抑制;线粒体△Ψ由(94.41±8.17)%下降到(30.70±8.01)%(P<0.05);唾液酸含量由(0.33±0.06)mmol/L下降到(0.09±0.03)mmol/L(P<0.01);ROS水平由(52.48±6.09)%升高到(68.98±7.26)%(P<0.05)。结论:pIRApoptinHNIL18可通过线粒体途径诱导细胞凋亡,从而抑制人结肠癌细胞HCT-116的生长。     

Reduced receptor expression for platelet-derived growth factor and epidermal growth factor in dividing mouse lung epithelial cells.

The roles of growth factors in mouse lung neoplasia were investigated by examining receptors for platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) in epithelial cell lines. Whereas nontumorigenic lung cells expressed mRNA and protein for PDGF receptor (PDGFR)-alpha, PDGFR-beta, and EGF receptor (EGFR), five of six neoplastic lines did not. Because this exceptional tumorigenic cell line grows slowly, we hypothesized that receptor levels increased with cell stasis. To test this hypothesis, serum concentrations were manipulated, and log-phase and post-confluent cells were compared. Consistent with our hypothesis, PDGFR-alpha and EGFR contents, but not PDGFR-beta contents, increased at stasis. Ki-ras mutation initiates lung tumorigenesis in mice, but activation of Ki-ras did not affect receptor expression. This was determined both by transfecting nontumorigenic cells with activated Ki-ras and neoplastic cells with a Ki-ras antisense construct and by diminishing Ki-ras activation by using a farnesyltransferase inhibitor. Stasis-associated upregulation of growth-factor receptor expression suggests a function in lung cell differentiation that is abrogated during neoplastic growth.     

Heparin-binding epidermal growth factor-like growth factor isoforms and epidermal growth factor receptor/ErbB1 expression in bladder cancer and their relation to clinical outcome

BACKGROUND: Cleavage of membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields a soluble HB-EGF isoform (sHB-EGF), which is an activating epidermal growth factor receptor (EGFR) ligand and a C-terminal fragment HB-EGF-C acting directly in the nucleus. In bladder cancer, overexpression of both HB-EGF and EGFR have been observed, but to the authors' knowledge the prognostic significance of different modes of HB-EGF signaling have remained unclear. METHODS: Expression and intracellular localization of HB-EGF and EGFR were examined by immunohistochemistry in paraffin-embedded specimens from 121 patients who underwent cystectomy for bladder cancer. Tumor stage was pTis/pT1 in 7 patients, pT2 in 41 patients, pT3 in 55 patients, and pT4 in 18 patients. Lymph node metastases were present in 32 patients. RESULTS: Using an antibody directed against the C-terminal domain, HB-EGF expression was detected in the cytoplasm or in the nucleus of tumor cells. EGFR staining was uniform at the plasma membrane. The actuarial 5-year cancer-specific survival of patients with tumors with predominant nuclear HB-EGF staining was 28% compared with 57% if HB-EGF staining was predominantly cytoplasmic (P = .027). Disease outcome of patients with a 'mixed' HB-EGF staining pattern was found to be between that of the 2 former groups. In agreement with previous studies, strong EGFR expression was associated with poor prognosis. Despite strong EGFR expression, predominant cytoplasmic HB-EGF staining was associated with a more favorable outcome, whereas a predominant nuclear pattern defined a subgroup with extremely poor prognosis (5-year tumor-specific survival of 55% vs 13%, respectively; P = .026). CONCLUSIONS: The current study results confirm that EGFR expression is significantly correlated with disease-specific mortality but that the outcome is also influenced by the mode of HB-EGF signaling. Additional nuclear HB-EGF signaling, indicative of increased cleavage of proHB-EGF, appears to enhance the adverse activities. Cytoplasmic HB-EGF staining likely reflects proHB-EGF, which may also exert antiproliferative effects.     

Microvessel density and p53 mutations in advanced-stage epithelial ovarian cancer

We planned to determine the relationship between angiogenesis and p53 mutational status in advanced-stage epithelial ovarian cancer. Using 190 tumor samples from patients with stage III and IV ovarian cancer we performed p53 sequencing, immunohistochemistry, and CD31 microvessel density (MVD) determination. MVD was elevated in tumors with p53 null mutations compared to p53 missense mutation or no mutation. Disease recurrence was increased with higher MVD in both unadjusted and adjusted analyses. In adjusted analysis, p53 null mutation was associated with increased recurrence and worse overall survival. Worse overall survival and increased recurrence risk were also associated with the combination of CD31 MVD values >25 vessels/HPF and any p53 mutation. P53 mutation status and MVD may have prognostic significance in patients with advanced-stage ovarian cancer. Tumors with p53 null mutations are likely to be more vascular, contributing to decreased survival and increased recurrence probability.     

EGFR在非小细胞肺癌中的表达及临床意义

目的：探讨表皮生长因子受体（EGFR）在非小细胞肺癌（NSCLC）中的表达及其与NSCLC发生、发展及预后的关系,指导非小细胞肺癌的靶向治疗。方法：回顾性分析82例NSCLC手术病例临床病理资料及随访资料,用免疫组化（EnVision法）的方法观察EGFR在非小细胞肺癌组织中的表达,对比分析20例非恶性肺组织中EGFR的表达。结果：EGFR在NSCLC中的表达率为53.66%,在非恶性肺组织中EGFR均呈阴性表达;EGFR在NSCLC中的表达与患者的性别、病理类型、TNM分期及淋巴结转移有显著统计学意义（P〈0.05）;EGFR高表达者生存期短。结论：EGFR在NSCLC中高表达;女性患者高于男性,并且与患者的病理类型、TNM分期及淋巴结转移有密切的关系,可作为判断NSCLC患者病情进展及预后的重要指标,还可以指导NSCLC患者的靶向治疗。     

Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer

Epidermal growth factor receptor (EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer (CRC). Evidence from clinical trials indicates that cetuximab and panitumumab (anti-EGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS (KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade.     

上皮性卵巢癌组织中肺耐药蛋白的表达及意义

目的探讨上皮性卵巢癌中肺耐药蛋白(LRP)的表达及其临床意义。方法采用免疫组化SP法及半定量分析方法,检测上皮性卵巢癌64例,复发后二次手术癌组织17例,卵巢良性上皮性肿瘤16例及正常卵巢组织14例中LRP的表达,并进行相关临床病理因素分析。结果在上皮性卵巢癌中LRP的阳性率为78.1%,与卵巢良性肿瘤及正常卵巢有显著性差异(P<0.01);化疗后癌组织中LRP的强阳性表达率与初治卵巢癌组织中相应的表达率差异有显著性。结论LRP在上皮性卵巢癌中较恒定表达,化疗可以增加癌组织中LRP的表达。检测LRP表达水平可以预测卵巢癌对铂类联合化疗疗效,也是判断其预后的可靠指标之一。