卵巢上皮性癌组织ERβ和ERK1/2表达及其相关性分析

目的:探讨ERβ和ERK1/2在卵巢上皮性癌组织中的表达及其相关性。方法:采用RT-PCR检测70例卵巢上皮性癌、24例卵巢良性肿瘤、24例正常卵巢组织中ERβ和ERKl/2 mRNA的表达,并分析其与临床病理特征之间的关系及两者的相关性。结果:卵巢上皮性癌组织中ERβ阳性表达率为55.7%,显著低于卵巢良性肿瘤(91.7%)及正常卵巢组织(100.0%),P<0.05;ERK1与ERK2的阳性表达率分别为85.7%和85.7%,显著高于卵巢良性肿瘤(50.0%和50.0%)及正常卵巢组织(33.3%和33.3%),P<0.05;卵巢良性肿瘤与正常卵巢组织相比,ERβ和ERK1/2表达差异无统计学意义,P>0.05。ERβ阳性表达率与组织学类型、组织分化程度及淋巴转移相关,P<0.05;与患者年龄、FIGO分期及腹水无关,P>0.05。ERK1/2阳性表达率与组织分化程度、FIGO分期和腹水相关,P<0.05;与患者年龄、组织学类型及淋巴转移无关,P>0.05。在卵巢上皮性癌组织中,ERβ和ERK1/2表达呈负相关,r值分别为-0.743和-0.832,P值分别为0.009和0.001。结论:卵巢上皮性癌组织中ERβ表达的降低和ERK1/2的过高表达可能在卵巢癌发生、发展和侵袭中有协同作用,这可能为卵巢癌的预后和内分泌治疗提供新的靶点和方向。     

上皮性卵巢癌组织E-cadherin mRNA表达临床意义的研究

目的:研究E-钙黏附蛋白(E-cadherin,E-cad)mRNA在正常卵巢、上皮性卵巢良性肿瘤及上皮性卵巢癌组织中的表达,并探讨E-cad表达与上皮性卵巢癌临床病理特征的关系。方法:用荧光定量-PCR法(FQ-PCR)分别检测正常卵巢上皮组织、卵巢上皮性良性肿瘤以及上皮性卵巢癌组织中E-cad的表达水平。结果:E-cad在10例正常卵巢上皮组织中表达为0,阳性表达率0;在10例良性卵巢上皮性肿瘤组织中阳性表达为0.261 7±0.138 2,阳性表达率为100%;在30例恶性卵巢上皮性肿瘤组织中阳性表达为0.012 7±0.018 1,阳性表达率为50%;3组间比较差异有统计学意义,χ2=30.924,P<0.05。E-cad的表达与FIGO分期成负相关,r=-0.873,P<0.05;与患者的生存时间呈正相关,r=0.602,P<0.05。E-cad表达与其组织学类型无相关性,χ2=3.811,P>0.05;与病理分级无相关性,χ2=3.458,P>0.05。结论:E-cad可作为上皮性卵巢癌病情进展和预后判断的指标之一,为分子靶向治疗提供一个依据。     

Lewisy抗原及IGF-1R在卵巢黏液性肿瘤中的表达及意义

目的：探讨Lewis y抗原及胰岛素样生长因子受体-1（IGF-1R）在卵巢黏液性肿瘤中表达规律及其相关性。方法：用免疫组化法检测62例卵巢黏液性肿瘤和20例正常卵巢组织中Lewis y抗原与IGF-1R的表达,并分析其表达与卵巢癌病理分级、临床分期及淋巴结转移的关系。结果：Lewis y在恶性、交界性、良性和正常组的阳性表达率分别是90.0%、70.6%、53.3%和0%,呈下降趋势,其中恶性与交界性,良性和正常组比较差异有统计学意义（P〈0.05）;IGF-1R在恶性、交界性、良性和正常组的阳性表达率分别是93.3%、70.6%、46.7%和40.0%,呈下降趋势,其中恶性与交界性,良性和正常组比较差异有统计学意义（P〈0.05）;Lewis y抗原或IGF-1R的阳性表达率与卵巢黏液癌临床病理参数无关（P均〉0.05）;Lewis y抗原和IGF-1R的表达水平随临床分期的增加,但无统计学意义（P〉0.05）、随分化程度的降低而增加（P〈0.05）,与有无淋巴结转移无关（P〉0.05）;Lewis y抗原和IGF-1R在卵巢黏液性囊腺癌中的表达呈显著正相关（r=0.711,P〈0.005）。结论：随着卵巢黏液性肿瘤的恶性进展Lewis y抗原及IGF-1R的表达上调,且两者的表达呈显著性正相关。提示Lewis y抗原及IGF-1R对卵巢黏液性囊腺癌的转移、分化起促进作用。     

HMGN5蛋白在上皮性卵巢恶性肿瘤中的表达及意义

目的:探讨高迁移率族核小体结合域5(high mobility group nucleosome 5,HMGN5)蛋白在上皮性卵巢恶性肿瘤中的表达及其临床意义。方法:本研究共纳入手术切除组织石蜡标本50例,采用免疫组化方法检测上皮性卵巢恶性肿瘤标本35例、上皮性卵巢良性肿瘤标本15例中HMGN5蛋白的表达情况,并分析HMGN5蛋白阳性表达率与上皮性卵巢恶性肿瘤临床病理特征之间的关系。结果:HMGN5蛋白在上皮性卵巢恶性肿瘤组织中的阳性表达率明显高于上皮性卵巢良性肿瘤组织,差异有统计学意义（P＜0.05）;HMGN5蛋白在上皮性卵巢恶性肿瘤组织中的阳性表达率与年龄、有无腹水、是否为浆液性上皮性癌无关（P＞0.05）,而与组织分化程度、手术病理分期有关（P＜0.05）。HMGN5蛋白在中低分化上皮性卵巢恶性肿瘤组织中的阳性表达率明显高于高分化上皮性卵巢恶性肿瘤组织,差异有统计学意义（P＜0.05）;HMGN5蛋白在手术病理分期为Ⅲ-Ⅳ期上皮性卵巢恶性肿瘤组织中的阳性表达率明显高于Ⅰ-Ⅱ期上皮性卵巢恶性肿瘤组织,差异有统计学意义（P＜0.05）。结论:HMGN5蛋白可能在上皮性卵巢恶性肿瘤的发生以及恶性进展中发挥作用,对上皮性卵巢恶性肿瘤的诊断及病情评估有一定价值,有可能是上皮性卵巢恶性肿瘤治疗的一个潜在靶点。     

Lewis y抗原及IGF-1R 在卵巢黏液性肿瘤中的表达及意义

目的:探讨Lewis y抗原及胰岛素样生长因子受体-1(IGF-1R)在卵巢黏液性肿瘤中表达规律及其相关性.方法:用免疫组化法检测62例卵巢黏液性肿瘤和20例正常卵巢组织中Lewis y抗原与IGF-1R的表达,并分析其表达与卵巢癌病理分级、临床分期及淋巴结转移的关系.结果:Lewis y 在恶性、交界性、良性和正常组的阳性表达率分别是90.0%、70.6%、53.3%和0%,呈下降趋势,其中恶性与交界性,良性和正常组比较差异有统计学意义(P<0.05);IGF-1R在恶性、交界性、良性和正常组的阳性表达率分别是93.3%、70.6%、46.7%和40.0%,呈下降趋势,其中恶性与交界性,良性和正常组比较差异有统计学意义(P<0.05);Lewis y抗原或IGF-1R的阳性表达率与卵巢黏液癌临床病理参数无关(P均>0.05); Lewis y抗原和IGF-1R的表达水平随临床分期的增加,但无统计学意义(P>0.05)、随分化程度的降低而增加(P<0.05),与有无淋巴结转移无关(P>0.05);Lewis y抗原和IGF- 1R在卵巢黏液性囊腺癌中的表达呈显著正相关 (r=0.711,P<0.005).结论:随着卵巢黏液性肿瘤的恶性进展Lewis y抗原及IGF-1R的表达上调,且两者的表达呈显著性正相关.提示Lewis y抗原及IGF-1R对卵巢黏液性囊腺癌的转移、分化起促进作用.     

卵巢上皮性肿瘤组织Nectin-4表达临床意义的探讨

目的:探讨卵巢上皮性癌(卵巢癌)组织中Nectin-4 mRNA和蛋白的表达及其与临床病理参数之间的关系。方法:采用逆转录聚合酶链式反应(RT-PCR)技术,检测30例卵巢癌、25例卵巢上皮性肿瘤和30例正常卵巢组织中Nectin-4 mRNA的表达情况;采用免疫组织化学法检测Nectin-4蛋白的表达情况,并分析其与卵巢癌临床病理参数的关系。结果:卵巢癌组Nectin-4 mRNA表达水平为0.71±0.12,卵巢良性肿瘤组为0.32±0.09,正常卵巢组为0.30±0.09,卵巢癌组的mRNA表达量显著高于后两组,差异有统计学意义,P<0.01。卵巢癌组Nectin-4蛋白表达水平为3.35±0.52,卵巢良性上皮性肿瘤组1.36±0.41,正常卵巢组1.15±0.44,卵巢癌组织的Nectin-4蛋白表达量明显高于卵巢良性上皮性肿瘤和正常卵巢组织,差异有统计学意义,P<0.01。卵巢癌组织中Nectin-4 mRNA和蛋白表达水平,在不同年龄、不同病理类型间比较,差异均无统计学意义,P>0.05;而在不同病理分化程度、手术分期及有无淋巴结转移间比较,差异均有统计学意义,P<0.05。结论:Nectin-4 mRNA和蛋白在卵巢癌组织中均呈高表达,而在卵巢良性肿瘤组织和正常卵巢组织中仅有微量表达。在卵巢癌组织中,其表达程度与病理分化程度、手术病理分期及淋巴结转移有密切关系。     

卵巢上皮性肿瘤中基质金属蛋白酶MMP-9及其组织抑制剂TIMP-1 mRNA的表达及意义

目的:探讨基质金属蛋白酶(MMP-9)及其组织抑制物(TIMP-1)mRNA与卵巢上皮性癌的发生、发展及侵袭、转移的关系.方法:采用RT-PCR技术检测38例卵巢上皮性癌、15例卵巢交界性上皮性肿瘤、16例卵巢良性上皮性肿瘤及11例正常卵巢组织中MMP-9及TIMP-1 mRNA的表达,并分析其与各临床病理参数的关系.结果:MMP-9 mRNA在卵巢上皮性癌及卵巢交界性上皮性肿瘤组织中的阳性表达率分别为76%、44%及表达水平(分别为154.14±4.42,96.87±3.04)均显著高于卵巢良性上皮性肿瘤及正常卵巢组织(分别为13%,9%和8.26±2.67,2.341.02;P均＜0.05);且MMP-9mRNA在晚期卵巢上皮性癌组织中的阳性表达率和表达水平明显高于早期(P＜0.05).TIMP-1 mRNA在卵巢上皮性癌及卵巢交界性上皮性肿瘤组织中的阳性表达率(分别为68%,38%)及表达水平(分别为126.35±3.81,90.62±5.54)均显著高于卵巢良性上皮性肿瘤及正常卵巢组织(分别为13%,9%和8.32±2.02,2.63±1.35;P均＜0.05);TIMP-1mRNA在卵巢上皮性癌组织中的阳性表达率和表达水平与各临床病理参数均无相关性(P＞0.05).结论:MMP-9mRNA的高表达及MMP-9/TIMP-1平衡的调节失衡导致卵巢上皮性肿瘤的发生、发展;MMP-9mRNA的高表达对卵巢上皮性癌的预后有意义.     

IGF-Ⅱ、VEGF和MVD在肝细胞癌中的表达及临床意义

目的探讨胰岛素样生长因子Ⅱ(IGF-Ⅱ)、血管内皮生长因子(VEGF)以及CD34抗体标记肿瘤微血管密度(MVD)在人原发性肝细胞癌(HCC)中的表达水平、临床意义及其相关性。方法应用免疫组织化学法检测50例HCC患者手术切除肝癌组织和癌旁组织标本中IGF-Ⅱ、VEGF和CD34的表达,分别对IGF-Ⅱ和VEGF表达进行积分光密度值(IOD)测定,对CD34阳性组织进行MVD计数,并结合临床资料进行统计学分析。结果 IGF-Ⅱ在HCC肝癌组织、癌旁组织和正常肝组织中的IOD值分别为55940.00±44570.41、83688.81±64460.15和0;VEGF的IOD值分别为37315.79±27315.09、38181.70±33391.02和2528.96±1445.21。肝癌组织、癌旁组织与正常肝组织相比,IGF-Ⅱ和VEGF的IOD值差异均有统计学意义(P<0.05);但肝癌组织与癌旁组织比较,IGF-Ⅱ的IOD值差异有统计学意义(P<0.05),而VEGF的IOD值差异无统计学意义(P>0.05)。HCC肝癌组织MVD值为42.10±20.63,癌旁组织MVD值为28.96±8.55,正常肝组织MVD值为17.70±9.67,三者差异有统计学意义(P<0.01)。IGF-Ⅱ、VEGF和MVD的表达都与淋巴结或肝内转移、病理分化程度有关(P<0.05),而与其他因素无关(P>0.05);且IGF-Ⅱ与肿瘤大小有关(P<0.05)。IGF-Ⅱ和VEGF共阳性表达组MVD值为44.24±21.22,高于IGF-Ⅱ和VEGF共阴性表达组MVD值(19.25±14.45),差异有统计学意义(P<0.05)。且IGF-Ⅱ在HCC肝癌组织中的表达与VEGF呈明显正相关(P<0.01),随着IGF-Ⅱ强度的增加,VEGF表达增强。结论 IGF-Ⅱ在HCC中表达显著增加,并可能诱导VEGF和MVD的过表达,且与HCC的侵袭性生物学行为密切相关。     

IGF-ⅠTGF-β1在卵巢上皮性肿瘤中的表达及与微血管密度的关系

  目的  检测卵巢上皮性肿瘤中胰岛素样生长因子(IGF-Ⅰ)、转化生长因子(TGF-β1)的表达及肿瘤微血管密度(MVD), 分析其与卵巢癌临床病理特征的关系。  方法  收集天津市中心妇产科医院2005年12月至2010年5月间诊治的卵巢癌35例, 交界性肿瘤31例, 良性肿瘤30例, 正常卵巢组织20例。通过免疫组织化学法检测IGF-Ⅰ及TGF-β1的表达与MVD。  结果  上皮性卵巢癌中IGF-Ⅰ及TGF-β1的表达显著高于交界性肿瘤、良性卵巢肿瘤和正常卵巢组织(P < 0.05);1GF-Ⅰ与卵巢癌组织学分级及腹水形成相关(P < 0.05), TGF-β1与腹水形成相关(P < 0.05);MVD与临床分期、组织分级、腹水形成相关(P < 0.05)。IGF-Ⅰ和TGF-β1在各组中的表达存在正相关(r=0.68, P < 0.05);IGF-Ⅰ、TGF-β1的表达与MVD均值存在显著正相关(r=0.45, P=0.01;r=0.39, P=0.02);IGF-Ⅰ、TGF-β1阳性组无瘤生存率及总生存率均有下降的趋势, 但差异无统计学意义(P>0.05)。  结论  上皮性卵巢癌中, IGF-Ⅰ、TGF-β1的表达与MVD呈正相关。IGF-Ⅰ、TGF-β1和MVD形成在上皮性卵巢癌的发病机理中起着重要作用。      

酪氨酸激酶受体B在卵巢上皮性癌中的表达及其意义

背景与目的: 失巢凋亡抑制因子酪氨酸激酶受体B(tyrosine kinase receptor,TrkB)能诱导正常上皮细胞的恶性转化并且使该细胞具有高转移能力.TrkB在良性肿瘤中及正常卵巢上皮中不表达,在癌组织中不但表达,并且与交界性肿瘤比较表达明显增高;转移灶和低分化癌组织中明显增高,如在神经母细胞瘤和其它多种人类高侵袭性恶性肿瘤组织中过度表达,本研究旨在探讨其过度表达与肿瘤组织分化及病人预后的关系.方法: 选取卵巢癌石蜡标本73例(包括与原发灶相对应的8例腹水中的癌细胞团簇),其中低分化腺癌34例,28例卵巢交界性上皮性肿瘤;16例卵巢良性上皮性肿瘤及13例正常卵巢组织作为对照,行免疫组化ABC法检测TrkB的表达:随机选取上述病例中30例(包括4例与原发灶相对应的火网膜转移灶和腹水中的癌细胞团簇)、交界性上皮性肿瘤7例;卵巢良性上皮性肿瘤4例及正常卵巢组织(包括卵巢皮质和髓质)2例作为对照,行RT-PCR检测TrkB的表达.结果: RT-PCR结果表明,TrkB mRNA在卵巢癌与卵巢交界性肿瘤中的相对转录水平分别为(16.7±3.1)%和(4.6±0.4)%,在卵巢癌组织中表达明显增加(P<0.001);TrkB mRNA在大网膜转移灶和腹水中的癌细胞团簇中的TrkB mRNA相对表达量分别为(31.4±1.4)%和(28.2±0.7)%,与相应的原发灶(18.1±1.1)%比较,差异有显著性(P<0.001).免疫组化结果表明,卵巢良性上皮性肿瘤及正常卵巢上皮不表达TrkB;TrkB在卵巢上皮性癌及卵巢交界性上皮性肿瘤组织中的阳性表达率分别为67.12%(49/73)和14.29%(4/28),两者比较差异有显著性(P<0.001),TrkB前体蛋白(表达于胞质)广泛地高表达于卵巢上皮性癌组织中67.12%(49/73),全长TrkB蛋白(表达于胞膜)在腹水中的癌细胞团簇100%(8/8)和低分化卵巢癌组织中100%(34/34)表达增强,与原发灶49.32%(36/73)和高分化癌7.69%(3/39)比较,差异有显著性(P<0.01).TrkB阳性表达与卵巢癌患者不良预后有关(P<0.002).结论: 卵巢上皮性痛中存在TrkB的过度表达;全长TrkB高表达于低分化卵巢癌和腹水中的癌细胞团簇中,TrkB可能是介导卵巢癌失巢凋亡抑制的因子;TrkB的过度表达预示卵巢癌的不良预后.     

Oxaliplatin and ovarian cancer

Oxaliplatin was brought into clinical evaluation in ovarian cancer because of the in vitro and in vivo antitumor activity observed in experimental models resistant to cisplatin. As single agent at 130 mg/m2 every 3 weeks, the objective response rates rage from 16% to 29% in patients treated after failure of one or two regimens. As first line, in a randomized trial cyclophosphamide-cisplatin versus cyclophosphamide-oxaliplatine, no significant statistical differences were observed in efficacy parameters (response rate, progression free survival and overall survival). The toxicity profile seemed to favor the oxaliplatin arm. Many associations with other available active drugs as taxanes, gemcitabine and liposomal doxorubicin were performed with promising results.     

微小RNA与卵巢癌

微小RNA (miRNA)的异常表达与卵巢癌的发生发展密切相关,其参与调控卵巢癌的发生、侵袭和转移以及抗癌药物耐药性形成等过程.作为一种重要的生物学标志物,miRNA有望成为卵巢癌早期诊断与预后判断的新靶点,为卵巢癌的治疗提供新的途径.     

Angiogenesis and ovarian cancer

Ovarian carcinoma is the most important cause of gynaecological cancer-related mortality in Western societies. The age at diagnosis, extent of disease (as expressed by FIGO state), success of primary surgery and the histopathological features of the tumour are important prognostic markers. The majority of patients with ovarian cancer present with advanced disease (FIGO stage III/IV) and in this group of patients the median survival is only three years. New treatment approaches are therefore required to improve outcome in this disease. Angiogenesis, the development of a neovascular blood supply, is a critical step in the propagation of malignant tumour growth and metastasis and represents a promising target. This review will focus on angiogenesis, VEGF biology and the potential value of angiogenic factors with prognostic value in ovarian cancer.     

Endometriosis and ovarian cancer

Endometriosis is the leading cause of morbidity among premenopausal women and the complex pathogenesis of this disease remains controversial despite extensive research. This disease represents one of the most common gynecological problems. It is generally believed that this disease is due primarily to retrograde menstruation or transplantation of shed endometrium. Based on overwhelming data, ovarian endometrioma is considered a neoplastic process, since most endometriosis-associated ovarian carcinoma occur in the presence of atypical ovarian endometriosis. A study comparing patients with typical epithelial ovarian cancer with endometriosis-associated ovarian cancer demonstrated that the patients with the latter disease strongly differ in both biological and histological characteristics. The prevelance of this disease is not completely established, but approximately 15 percent of women suffer from this disease. In addition, we know about the possible links between endometriosis and cancer for almost 100 years. Despite clear evidence revealing that endometriosis increases ovarian cancer risks, it is possible that it may not affect disease progression after the appearance of ovarian cancer. However, despite clear evidence revealing that endometriosis increases ovarian cancer risk, our knowledge of the risk factors is far from established. In our review, we focused on the most recent approaches including possible biomarkers and genetic approaches.     

Docetaxel and ovarian cancer

Docetaxel has exhibited substantial clinical activity against platinum, refrac- tory, paclitaxel resistant and previously untreated advanced ovarian cancer. As single agent, in advanced ovarian cancer patients previously treated with platinum agents, docetaxel 100 mg/m(2) every 3 weeks yields a 30% overall response rate and 6 months duration of response. In vitro data demonstrate a lack of complete cross-resistance bet- ween docetaxel and paclitaxel. In both platinum- and paclitaxel-pretreated patients, the highest response rates were obtained in patients with the longest interval of time since receipt of prior chemotherapy. Docetaxel currently is being intensively evaluated as a component of first line combination chemotherapy for ovarian cancer. Phase I-II have shown that docetaxel-platinum doublets are feasible and highly effective in the treatment of ovarian cancer, with docetaxel-carboplatin providing a more favorable safety profile compared with docetaxel-cisplatin, particularly with respect to neurotoxicity. The preliminary results of a phase III comparison of docetaxel-carboplatin versus paclitaxel-carboplatin support the clinical use of docetaxel-carboplatin as first line chemotherapy for stage IC to IV ovarian cancer, as it was shown to reduce the incidence of grade > 2 neurosensory toxicity compared to paclitaxel-carboplatin. Comparative overall survival and quality of life and more mature progression free survival data will be instrumental in determining the relative merits of docetaxel-carboplatin and paclitaxel-carboplatin as first line adjuvant therapy for ovarian cancer. The positive clinical experiences with docetaxel-provide a strong basis for continued investigation of docetaxel-carboplatin-based chemotherapy as component of advanced ovarian cancer management.     

Use of hormone replacement therapy before and after ovarian cancer diagnosis and ovarian cancer survival

Use of hormone replacement therapy (HRT) has been hypothesized to affect survival of epithelial ovarian cancer (EOC). We studied 5-year survival in patients with invasive EOC and borderline ovarian tumors (BOT) according to HRT use before and after diagnosis in a prospective nation-wide cohort study of 799 women diagnosed with EOC (n = 649) and BOT (n = 150) aged 50-74 years in 1993-1995 in Sweden. Cox regression was used to obtain multivariate age-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Multivariate models included indicator variables for age, tumor stage, grade and histological subtype. After 5 years of follow-up, 45% of the patients with EOC and 93% of the patients with BOT were alive. For women with BOT there were no associations between HRT-use pre- or postdiagnosis and survival. There was no overall difference in 5-year EOC survival according to use HRT before diagnosis (multivariate HR = 0.83, 95% CI = 0.65-1.08), except for serous EOC (HR = 0.69, 95% CI = 0.48-0.98). Analyses of different HRT preparations, duration and recency of use did not reveal any variations in pattern of survival. We observed a better survival for EOC-patients who used HRT after diagnosis (multivariate HR = 0.57, 95% CI = 0.42-0.78). We conclude that HRT-use prior to diagnosis of EOC does not affect 5-year survival, except for a possible survival advantage in serous EOC. Women using HRT after diagnosis had a better survival than women with no use, but we cannot rule out that this latter finding may reflect a subtle selection process.