微小染色体维持蛋白5基因在卵巢上皮性肿瘤中的表达与意义

目的:探讨微小染色体维持蛋白5(MCM5)基因在卵巢上皮性肿瘤中的表达及其意义。方法:采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法分别半定量检测MCM5mRNA和MCM5蛋白在正常卵巢、卵巢上皮性肿瘤组织中的表达。结果:MCM5mRNA和蛋白在不同卵巢组织中的表达趋势是一致的,上皮性癌组织中的表达高于正常和上皮性良性肿瘤组织,差异有统计学意义(P<0.05)。MCM5mRNA和蛋白在不同年龄组、不同病理类型的肿瘤中表达差异无统计学意义(P>0.05)。MCM5mRNA和蛋白的表达水平随组织学级别的升高而升高,在低分化(G3)上皮性癌中的表达高于高分化(G1)和中分化(G2)癌,差异有统计学意义(P<0.05)。结论:MCM5的表达可能参与卵巢上皮性癌的发生发展过程,其表达水平与肿瘤的分化程度有关,可能做为新的卵巢肿瘤增生标志物。     

EGFR、VEGF及LRP mRNA在卵巢上皮性癌组织中的表达及其意义

目的:探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)和肺耐药蛋白(lung resistanceprotein,LRP)mRNA在卵巢癌的表达及意义。方法:用逆转录聚合酶链反应(RT-PCR)技术检测15例正常卵巢、13例卵巢良性肿瘤及51例卵巢上皮癌组织中EGFR mRNA、VEGF mRNA和LRP mRNA的表达,并分析它们的相关性。结果:卵巢上皮癌组织中EG-FR、VEGF和LRP阳性表达率显著高于正常卵巢及卵巢良性肿瘤组织(P<0.05);EGFRmRNA表达与卵巢上皮癌手术病理分期有关,Ⅲ~Ⅳ期的阳性表达率及表达强度高于Ⅰ~Ⅱ期(P<0.05);VEGF mRNA表达与卵巢上皮癌手术病理分期及淋巴结转移有关,Ⅲ~Ⅳ期和有淋巴结转移组的表达强度分别高于Ⅰ~Ⅱ期和无淋巴结转移组(P<0.05);LRP mRNA表达与卵巢上皮癌患者年龄、临床分期、分化程度、病理类型及淋巴结转移等临床病理参数无关(P>0.05);EGFR和VEGF基因之间(r=0.460,P<0.05)、EGFR和LRP基因之间表达显著相关(r=0.749,P<0.01)。结论:EGFR与卵巢癌血管生成和化疗耐药产生有关,可能参与了卵巢癌的发生发展,检测卵巢癌EGFR、VEGF和LRP可能对靶向化疗有指导作用。     

NGAL和MMP-9在卵巢上皮性癌中的表达及相关性研究

目的:检测中性粒细胞明胶酶相关载脂蛋白(NGAL)和基质金属蛋白酶-9(MMP-9)在卵巢上皮性肿瘤组织和血清中的表达,了解两者与卵巢癌临床病理特征的关系。方法:应用半定量RT-PCR和ELISA法检测50例上皮性卵巢癌、21例卵巢良性肿瘤和18例正常对照的卵巢组织和血清中NGAL和MMP-9的表达水平。结果:(1)卵巢癌组的组织及血清中NGAL和MMP-9表达明显高于卵巢良性肿瘤组和正常对照组(P均<0.05);二者的高表达与临床分期、淋巴结转移正相关(P均<0.05);卵巢癌患者的组织及血清中NGAL与卵巢癌的组织分化程度正相关(P均<0.05),MMP-9则与卵巢癌的组织分化程度负相关(P均<0.05)。(2)卵巢癌患者的组织或血清中,NGAL表达均与MMP-9表达呈正相关(r=0.740,r=0.676,P均<0.05)。结论:NGAL和MMP-9在卵巢上皮性癌中表达上调,可能与卵巢上皮性癌的发生、发展有关。     

AQP4,5在卵巢上皮性肿瘤的表达及意义

目的:探讨水通道蛋白4,5(AQP4,5)在卵巢上皮性肿瘤的表达及意义。方法:原位杂交和免疫组化染色检测AQP4 mRNA及蛋白在10例正常卵巢组织、15例卵巢良性上皮性肿瘤、15例卵巢交界性上皮性肿瘤及50例卵巢恶性上皮性肿瘤的分布和表达。结果:AQP4,5 mRNA及蛋白主要于交界性及恶性上皮性肿瘤细胞的胞质和胞膜表达。AQP4,5在恶性及交界性上皮性肿瘤的表达量明显高于良性上皮性肿瘤及正常卵巢组织(P0.05),良性上皮性肿瘤与正常卵巢组织间的表达差异无统计学意义(P0.05)。卵巢癌有腹水者AQP4,5表达量明显高于无腹水者(P0.05)。组织学分级为G2、G3的卵巢癌组织中AQP4,5表达高于G1;Ⅲ、Ⅳ期卵巢癌AQP4表达明显高于Ⅰ、Ⅱ期(P0.05);伴淋巴转移者AQP4明显高于无淋巴转移者(P0.05)。AQP4,5蛋白及mR-NA表达有相关性(P0.05,r=0.487)。结论:AQP4,5高表达可能通过增加肿瘤细胞对水的通透性,在卵巢上皮性肿瘤的发生及进展中起重要作用,并且可能参与卵巢癌腹水的形成。     

Notch3及Notch基因细胞内区在卵巢上皮性癌组织中的表达及DAPT对卵巢上皮性癌细胞的作用

目的 了解卵巢上皮性癌(卵巢癌)组织中Notch3及Notch基因细胞内区(NICD)蛋白的表达水平及其临床意义,探讨γ分泌酶抑制剂--氮-[氮-(3,5-二氟苯乙酰基)-L-丙氨酰]-S-苯基甘氨酸丁酯(DAPT)对卵巢癌细胞系OVCAR3、A2780细胞的作用.方法 (1)选取2006年7月到2009年6月在北京大学第一医院因卵巢癌接受手术治疗且临床病理资料完整的患者共58例,选取同期因子宫肌瘤或子宫腺肌病及其他非卵巢病变行子宫全切除+双侧附件切除术者共21例作为对照,采用蛋白印迹法检测卵巢癌及正常卵巢组织中NICD蛋白的表达水平,免疫组化法检测卵巢癌及正常卵巢组织中Notch3蛋白的阳性表达率,并对不同临床病理特征的卵巢癌组织中NICD和Notch3蛋白表达进行比较.(2)体外培养卵巢癌OVCAR3、A2780细胞,加入不同浓度(分别为0.1、1、5、10μmol/L)的DAPT,设仅加溶剂二甲基亚砜(DMSO)者为空白对照,采用蛋白印迹法检测DAPT处理后卵巢癌OVCAR3、A2780细胞中NICD蛋白表达水平的变化,四甲基偶氮唑蓝(MTT)比色法检测卵巢癌细胞的生长情况,流式细胞仪检测细胞增殖指数(PI)、S期细胞比例(SPF)和细胞凋亡率的变化.结果 (1)卵巢癌、正常卵巢组织中Notch3蛋白的阳性表达率分别为78%(45/58)、24%(5/21),两者比较,差异有统计学意义(P<0.01).卵巢癌、正常卵巢组织中NICD蛋白的表达水平分别为1.64±0.19、0.98±0.20,两者比较,差异有统计学意义(P<0.05).卵巢癌组织中,NICD蛋白的表达水平,病理分化程度为低分化者(1.90±0.22)明显高于高～中分化者(1.25±0.21,P<0.05),手术病理分期为Ⅲ～Ⅳ期者(1.80±0.21)明显高于Ⅰ期者(1.21±0.15,P<0.05),而不同病理类型和是否行新辅助化疗间比较,差异则无统计学意义(P>0.05);Notch3蛋白的阳性表达率,不同病理类型、手术病理分期、病理分化程度及是否行新辅助化疗间比较,差异均无统计学意义(P>0.05).(2)DAPT(5 μmol/L)处理不同时间(分别为24、48、72 h)后,OVCAR3、A2780细胞中NICD蛋白的表达水平均明显低于空白对照(P<0.05).不同浓度(分别为0.1、1、5、10 μmol/L)的DAPT处理不同时间(分别为0、6、12、24、36、48、72 h)后,OVCAR3、A2780细胞的生长均明显受抑制,分别与空白对照比较,差异均有统计学意义(P<0.05).不同浓度(分别为0.1、1、5、10 μmol/L)的DAPT处理不同时间(分别为24、48、72 h)后,OVCAR3、A2780细胞的SPF、PI明显下降,细胞凋亡率明显升高,分别与空白对照比较,差异均有统计学意义(P<0.05),且随着药物浓度的升高,出现这种作用的时间越早.结论 Notch3、NICD蛋白可能在卵巢癌的发生、发展中起一定的促进作用;DAPT能抑制卵巢癌细胞的增殖,促进卵巢癌细胞的凋亡,其机制可能与抑制NICD蛋白的生成有关.     

ERCC1基因mRNA表达水平在卵巢上皮性癌组织中的意义

目的:研究切除修复交叉互补基因1(ERCCI)在卵巢上皮性癌组织中的mRNA表达水平与患者对铂类药物化疗反应及生存期的关系,并探讨ERCCl基因缺失第Ⅷ外显子变异剪接体的临床意义.方法:使用TRIZol试剂提取63例卵巢上皮性癌组织总RNA,逆转录为cDNA后,TaqMan实时荧光定量RT-PCR技术分别检测ERCC1基因及缺失第Ⅷ外显子变异剪接体的mRNA表达水平,并分析其与患者化疗反应和术后生存期的关系.结果:①ERCC1基因总mRNA和去除变异剪接体后ERCC1全长相对表达量在化疗敏感组的值均低于化疗耐药组,差异有统计学意义(P=0.013;P=0.009).②总ERCC1 mRNA和去除变异剪接体后ERCC1全长相对表达量在低水平表达组比高水平表达组的生存期更长,差异有统计学意义(P=0.012;P=0.008).结论:卵巢癌组织中ERCC1基因mRNA表达水平能够预测患者的化疗反应性与术后生存期,缺失第Ⅷ外显子变异剪接体与患者的化疗反应和术后生存期没有关系,无临床意义,是无功能的转录产物.     

IGF1、IGF1R及IGFBP3在卵巢上皮性肿瘤的表达及临床病理意义

目的:探讨胰岛素样生长因子1(IGF1)及其受体(IGF1R)、胰岛素样生长因子结合蛋白质3(IGFBP3)在卵巢上皮性肿瘤的表达及在原发性卵巢上皮性癌(EOC)中的临床病理意义。方法:用免疫组化法检测10例正常卵巢组织、13例良性卵巢上皮性肿瘤、12例交界性卵巢上皮性肿瘤、50例EOC手术病理标本中IGF1、IGF1R、IGFBP3的表达,分析三者表达与EOC临床病理特征的相关性。结果:(1)IGF1、IGF1R、IGFBP3在正常卵巢组织、良性卵巢上皮性肿瘤、交界性卵巢上皮性肿瘤、EOC的表达依次增强,IGF1阳性表达率分别为20.00%,23.08%,25.00%,80.00%;IGF1R阳性表达率分别为20.00%,30.77%,33.33%,84.00%;IGFBP3阳性表达率分别为30.00%,38.46%,41.67%,86.00%,三者在EOC组的阳性表达率均明显高于交界性卵巢上皮性肿瘤组(P<0.01)。(2)IGF1R在EOC中的表达阳性程度与病理学分级、临床分期、腹水/腹腔冲洗液阳性之间呈显著正相关(P<0.05);IGFBP3表达的阳性程度与临床分期呈显著的负相关(P<0.05)。(3)IGF1R在EOC中的表达程度与IGF1表达程度间呈显著的正相关(P<0.05)。结论:卵巢上皮性癌中存在IGF1、IGF1R、IGFBP3的过表达,三者共同参与了EOC的发生发展过程;IGF1R与EOC不良预后的重要临床病理指标间呈显著的正相关,IGF1R可作为卵巢上皮性癌基因靶向治疗的新靶点。     

卵巢上皮性癌组织中KiSS-1基因及其受体GPR54 mRNA的表达及其意义

目的探讨肿瘤转移抑制基因KiSS-1及其受体GPR54mRNA在卵巢上皮性癌组织中的表达及其意义。方法采用RT-PCR技术检测37例卵巢上皮性癌、15例卵巢交界性上皮性肿瘤、15例卵巢良性上皮性肿瘤及11例正常卵巢组织中KiSS-1基因及其受体GPR54mRNA的表达,并分析其与各临床病理指标的相关性。结果KiSS-1mRNA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%、60%)及表达水平(分别为0·82±0·09、0·80±0·10)均显著高于卵巢良性上皮性肿瘤及正常卵巢组织(分别为20%、18%和0·65±0·10、0·66±0·06;P均<0·05);且KiSS-1mRNA在卵巢上皮性癌组织中的阳性表达率和表达水平均与手术病理分期和淋巴结转移有明显相关性(P<0·05)。GPR54mRNA在卵巢上皮性癌、卵巢交界性上皮性肿瘤、卵巢良性上皮性肿瘤及正常卵巢组织中的阳性表达率(分别为70%、67%、60%和45%)及表达水平(分别为0·79±0·07、0·76±0·10、0·73±0·07和0·78±0·08)分别比较,差异均无统计学意义(P>0·05);GPR54mRNA在卵巢上皮性癌组织中的阳性表达率和表达水平与手术病理分期、病理分级、病理类型、淋巴结转移及腹水生成均无相关性(P>0·05)。结论KiSS-1基因及其受体GPR54可能在抑制卵巢上皮性癌浸润和转移的过程中起重要作用。     

TSLC1在卵巢上皮性癌的表达及临床意义

卵巢癌是女性生殖系统三大恶性肿瘤之一,其特点是早期易发生盆腹腔转移,而肿瘤的浸润和转移是导致患者死亡率增高的主要原因.     

血管内皮生长因子及其受体在卵巢上皮性癌组织中的表达

目的研究血管内皮生长因子(VEGF)及其受体(FLT1、FLK1)mRNA在卵巢上皮性癌组织中的表达及与临床病理因素的相关性。方法采用逆转录聚合酶链反应技术检测70例卵巢上皮性癌及22例卵巢良性肿瘤病变组织标本中VEGFmRNA及其受体FLT1mRNA及FLK1mRNA的表达。结果在良、恶性卵巢组织中均检测到VEGF121mRNA、165mRNA的表达,在卵巢上皮性癌组织中表达水平分别为(0.452±0.134,0.301±0.096)高于良性卵巢肿瘤[0.195±0.066(P=0.000),0.204±0.059(P=0.001)];在卵巢上皮性癌组织中,VEGF121mRNA表达高于VEGF165mRNA(P=0.000),而在良性卵巢肿瘤组织中两者表达水平差异无显著性(P=0.667)。FLT1mRNA、FLK1mRNA在部分卵巢上皮性癌组织中表达,分别为38.6%(27/70)和25.7%(18/70),而在良性卵巢肿瘤组织中未见表达。卵巢癌组织中VEGF121、VEGF165、FLT1、FLK1之mRNA表达与患者年龄、肿瘤体积、淋巴结转移、肿瘤分期之间无明显相关性。结论VEGF121、165及其受体FLT1、FLK1在卵巢上皮性癌的血管生成中起重要作用。     

细胞周期素D1蛋白在卵巢上皮性肿瘤中的表达及其意义

目的　研究细胞周期素D1(cyclinD1)在卵巢上皮性肿瘤中的表达及意义。方法　 1997～ 2 0 0 0年采用免疫组织化学SP法 ,检测恶性卵巢上皮性肿瘤、交界性肿瘤、良性肿瘤、正常卵巢组织cyclinD1的表达。结果　在恶性卵巢上皮性肿瘤 ,良性肿瘤 ,正常卵巢组织之间cyclinD1的表达差异有显著性 (P <0 0 1)。cyclinD1的表达率与组织分化程度和临床分期有显著相关性 (P <0 0 5 ) ,cyclinD1的过度表达见于组织分化差 ,肿瘤发病的晚期。结论　cyclinD1在卵巢癌组织中广泛存在 ,并与组织分化 ,临床分期有一定相关性 ,提示该基因在卵巢癌的发生、发展中起一定作用     

Expression and clinical significance of pepsinogen C in epithelial ovarian carcinomas

OBJECTIVES: To describe the endometrial appearance in postmenopausal breast cancer patients on tamoxifen and to assess a routine surveillance scheme for endometrial lesions. STUDY DESIGN: Three hundred and seventeen postmenopausal breast cancer women already on tamoxifen at the start of the study (group I) and 89 breast cancer women assessed before any tamoxifen intake (group II) underwent an initial and then yearly scans with transvaginal ultrasonography, followed by an hysteroscopy and biopsy for women with an endometrium thickened above 8mm. Endometrial thickness was also measured in 823 women with no breast cancer nor tamoxifen intake (group III). RESULTS: Initial mean endometrial thickness was 8.2mm in group I, 4.4mm in group II and 3.4mm in group III (P<0.001). Eighteen percent endometrial lesions were found in group I and 3.3% in group II. We observed a significant association between endometrial pathology and both cumulated dose and total duration. Polyps were the most frequent and first to appear pathology. Five cancers were detected in group I, and all of them had taken tamoxifen for more than 3 years. CONCLUSION: Our surveillance scheme could be lightened; an acceptable screening scheme might include a baseline assessment before the start of tamoxifen and, if normal, yearly screening after 3 years of tamoxifen therapy, yearly surveillance for women with an abnormal baseline assessment and immediate investigation for symptomatic women.     

Expression and clinical significance of apolipoprotein D in epithelial ovarian carcinomas

OBJECTIVE: Apolipoprotein D is a protein component of the human plasma lipid transport system but is also associated with a more favorable prognosis in women with breast cancer. This retrospective study was undertaken to examine the tumoral expression of apolipoprotein D in epithelial ovarian cancer and to analyze the possible correlation with tumor and patient characteristics as well as androgen receptors and their prognostic significance. METHODS: Immunohistochemical evaluation was used to examine apolipoprotein D expression in paraffin blocks from 68 epithelial ovarian carcinomas. RESULTS: A total of 18 (26.4%) tumors stained positively. No significant correlation was found between apolipoprotein D expression and patient or tumor characteristics and androgen receptor status. However, apolipoprotein D expression was significantly associated with prognosis in patients with residual tumor greater than 1 cm. Thus, patients with apolipoprotein-D-negative tumors had a poorer overall survival than those with apolipoprotein-D-positive tumors (P = 0.039). In addition, multivariate analysis demonstrated that apolipoprotein D expression was an independent prognostic factor with initial tumor size in this group of patients (P = 0.005). CONCLUSIONS: Our results led us to consider the existence of apolipoprotein D expression by a significative percentage of ovarian carcinomas, and this protein expression might be of clinical usefulness for identifying lesions with different evolution.     

Expression of MUC1 in primary and metastatic human epithelial ovarian cancer and its therapeutic significance

BACKGROUND: MUC1 is associated with cellular transformation and tumorigenicity and is considered as an important tumor-associated antigen (TAA) for cancer therapy. The objective of this study was to evaluate the patterns of MUC1 expression in primary tumors and metastatic lesions in the advanced stages of epithelial ovarian cancers (EOCs) and correlate the expression with clinicopathological features. METHODS: The expression of MUC1 was examined on frozen tissue sections from primary EOC (n=42), the matched metastatic lesions (n=30) and paraffin-embedded tissue sections from primary EOC (n=60), normal ovarian tissues (n=20) using immunohistochemistry (IHC) by monoclonal antibody (MAb) C595. RESULTS: The expression of MUC1 was found in 92% (39/42) of EOC and 90% (27/30) of the matched metastatic lesions in frozen tissue sections respectively while the expression of MUC1 was found in 95% (57/60) of EOC and 5% (1/20) of normal ovarian tissues in paraffin-embedded sections respectively. Most of the tumors showed moderate to strong intensity staining while normal ovarian tissues only showed weak intensity staining. The overexpression of MUC1 was significantly associated with various progression parameters such as tumor stage, grade, residual disease status and presence of ascites (P<0.05). CONCLUSIONS: MUC1 is overexpressed in above 90% of late stage of EOC and of metastatic lesions but not in normal ovarian tissues, and the high expression of MUC1 is correlated with EOC progression. MUC1 antigen may be a useful therapeutic target to prevent the development of incurable, recurrent metastatic EOC.     

卵巢上皮癌组织中MT1-MMP的表达及意义

目的　探讨膜型基质金属蛋白酶 - 1(membranetype - 1matrixmetalloproteinase,MT1-MMP)在卵巢上皮癌组织中的表达及其与肿瘤生物学行为和预后的关系。方法　用免疫组化SP法检测 5 6例卵巢上皮癌组织、 15例卵巢良性肿瘤组织以及 10例正常卵巢组织中MT1-MMP蛋白的表达。结果　 6 7 9%的卵巢上皮癌组织MT1-MMP表达阳性 ,卵巢良性肿瘤组织很少表达 (4/ 15 ) ,正常卵巢组织中几乎不表达 (1/ 10 ) ,差异有显著性 (P <0 0 1)。MT1-MMP的表达水平与临床分期、组织学分级以及淋巴结转移密切相关。在单因素生存分析中 ,MT1-MMP的表达与患者预后不良有关。但是 ,在多因素分析中 ,MT1-MMP的表达并不是一个相对独立的预后因素。结论　①MT1-MMP在卵巢上皮癌中异常高表达 ;②MT1-MMP表达促进卵巢癌的侵袭和转移 ,可作为判断卵巢癌恶性表型的有用指标 ;③MT1-MMP的阳性表达与患者不良预后有关。     

The clinical significance of EphA2 and Ephrin A-1 in epithelial ovarian carcinomas

OBJECTIVES: To examine the expressions of the protein and mRNA of EPHA2 and EphrinA-1 in epithelial ovarian carcinomas/ovarian cancer cell lines and explore their prognostic value. METHODS: To validate the immunohistochemical method, two ovarian cancer cell lines (OVCAR3 and SKOV3) were examined with RT-PCR, Western blot, and immunohistochemistry for EphA2 and EphrinA-1 expressions. Tumors from 118 patients with advanced epithelial ovarian cancer were then evaluated for EPHA2 and Ephrin A-1 protein expression, and frozen tissues from 30 cases were used for laser capture microdissection (LCM) assistant RT-PCR RNA analysis. RESULTS: 11 (9.3%), 67 (56.8%), 26 (22.0%), and 14 (11.9%) tumors demonstrated negative, weak, moderate, and strong EphA2 protein expressions, respectively, while 3 (2.5%), 67 (56.8%), 32 (27.1%), and 16 (13.8%) tumors were negative, weak, moderate, and strong for Ephrin A-1 protein expression, respectively. Variable amount of mRNA expression was observed in the 30 tumors analyzed by the method of LCM assistant RT-PCR. There was a trend for association between higher levels of either EphA2 or Ephrin A-1 expression and higher histological grade (P = 0.05 for both factors). No significant correlation between the expressions of EphA2 or Ephrin A-1 and age, histological type, and FIGO stage was observed. Patients with higher levels of EphA2 protein expressions had significantly shorter survival. Cox multivariate analyses revealed that residual tumor after surgery, histological type, and EphA2 protein expression were of independent prognostic significance. CONCLUSIONS: High level of EphA2 protein expression is significantly associated with a shorter patient survival and EphA2 receptor is a valuable prognostic marker for ovarian carcinoma.     

卵巢上皮性肿瘤中细胞周期素D1蛋白与p16蛋白的表达及其临床意义

目的　探讨细胞周期素D1蛋白 (cyclinD1)与 p16蛋白在卵巢上皮性肿瘤中的表达及临床意义。 方法　 1998年 1月至 2 0 0 0年 1月采用免疫组化SP法 ,检测恶性、交界性、良性卵巢上皮性肿瘤、正常卵巢组织中的cyclinD1蛋白和p16蛋白的表达。结果　cyclinD1蛋白、p16蛋白表达的阳性率分别为恶性 5 0 %和 4 0 %、交界性30 %和 5 0 %、良性卵巢上皮性肿瘤 0和 80 %、正常卵巢组织中 0和 90 %。恶性卵巢上皮性肿瘤与良性卵巢上皮性肿瘤及正常卵巢组织之间比较 ,cyclinD1蛋白的表达差异有显著性意义 (P <0 0 1) ,p16蛋白的表达差异有显著性意义 (P <0 0 5 )。在恶性程度较高 ,组织分化差 ,晚期的恶性卵巢上皮性肿瘤中cyclinD1蛋白表达率高 ,p16蛋白的表达率低。相关性分析显示 ,cyclinD1蛋白与 p16蛋白的表达呈负相关。 结论　cyclinD1蛋白的过度表达与 p16蛋白表达的缺失在恶性卵巢上皮性肿瘤的发生、发展中起一定作用 ,二者可能存在相互抑制机制。     

CCNB1在卵巢癌中的表达及意义

目的:探讨CCNB1在卵巢癌诊断和预后判断的作用。方法:通过Oncomine数据库分析并提取组织RNA,Real-time PCR法检测CCNB1在卵巢癌组织中的表达。通过在线数据库及分析工具"the Kaplan Meier plotter"(KM plotter)数据库的应用发掘CCNB1的预后价值。结果:Oncomine数据库中共有18个研究结果涉及正常卵巢组织和卵巢癌组织中的CCNB1的表达情况,全部显示CCNB1在卵巢癌中表达增高。本研究对9对配对的卵巢癌及其癌旁组织进行Real-time PCR,得到相同结果。在KM plotter数据库中的分析显示:无论是无进展生存期(PFS)或总生存期(OS),CCNB1 mRNA水平越高,卵巢癌患者的预后越差(HR1,P0.05)。且CCNB1 mRNA高水平在早于2期(包括2期)卵巢癌患者中提示预后较差,在晚于3期(包括3期)患者中CCNB1 mRNA水平与预后无明显相关性。结论:CCNB1在卵巢癌组织中表达升高,可作为提示预后差的卵巢癌的分子标记物。     

Expression and prognostic significance in epithelial ovarian cancer

BACKGROUND: Insulin-like growth factor binding protein-3 (IGFBP-3) is a glycoprotein with specific binding affinity to peptide hormones insulin-like growth factors (IGFs) which are potent mitogens for a variety of cells. IGFBP-3 can inhibit the activities of IGFs by interfering with the interaction between IGFs and their receptor IGF-IR. Epithelial ovarian cancer (EOC) tissues express IGFBP-3, IGFs and IGF-IR. Moreover, high levels of IGF-I and IGF-IR have been shown in epithelial ovarian cancer, and IGF-I stimulates the growth of ovarian cancer. METHODS: We measured IGFBP-3 levels in ovarian cancer tissues of 147 consecutive patients and we examined its association with clinical and pathological features of the disease and patient survival. The average age of the patients in the study was 55 years and the median follow-up time was 37 months. IGFBP-3 levels were measured in the tissue extracts by a commercial ELISA kit and non-parametric statistics and the Cox regression survival analysis were used to determine the associations of IGFBP-3 with clinical and pathologic variables as well as with patient survival. RESULTS: High IGFBP-3 levels resulted significantly associated with some of the favorable prognostic features of the disease, including early clinical stage (p=0.048), small size of residual tumor (p=0.007), and optimal debulking result (p=0.007). High IGFBP-3 was also associated with a significantly reduced risk for disease progression (RR=0.52, p=0.034) and we showed an inverse dose-dependent relationship between IGFBP-3 and disease progression-free survival (p=0.033). However, the association with disease progression-free survival was no longer statistically significant in a multivariate analysis. An association between IGFBP-3 and overall survival was not shown. CONCLUSIONS: This study suggest that IGFBP-3 may play a role in the progression of epithelial ovarian cancer.     

IGF1R在卵巢子宫内膜异位囊肿中的表达及意义

目的:检测IGF1R在正常子宫内膜及卵巢子宫内膜异位囊肿(EMs)患者异位内膜中的表达,并探讨其与疾病发生的关系。方法:免疫组化SP染色及Western blot法检测IGF1R在50例正常子宫内膜及55例卵巢EMs异位内膜中的表达情况,并根据月经周期对样本进行分期分析。构建IGF1R的反义寡核苷酸,转染至正常内膜的原代细胞,运用Ed U技术研究IGF1R对细胞增殖的影响。结果:免疫组化检测显示,IGF1R表达于正常内膜及EMs组织的腺上皮细胞质及胞膜,异位内膜中表达量较高(P=0.014)。增生期正常内膜及异位内膜中IGF1R的表达差异无统计学意义;分泌期异位内膜中IGF1R的表达量高于分泌期正常子宫内膜(P=0.036)。分泌期子宫内膜中IGF1R表达显著高于增生期子宫内膜,差异有统计学意义(P0.001)。Western blot检测结果显示,异位内膜中IGF1R表达量较正常内膜高(P0.05);增生期正常内膜和异位内膜中IGF1R表达量差异无统计学意义;分泌期正常子宫内膜和异位内膜中IGF1R表达量分别为(0.26±0.13)和(0.65±0.16),差异有统计学意义(P=0.023)。正常内膜的原代细胞中沉默IGF1R表达后,细胞增殖能力明显下降(P=0.014)。结论:IGF1R在异位内膜中的表达量较正常内膜高,并且参与异位内膜的细胞增殖,提示IGF1R可能通过促进异位内膜细胞的增殖参与EMs的发生发展。