NF-κB/p65和VEGF在卵巢上皮性肿瘤的表达及临床意义

目的:研究NF-κB/p65和VEGF在卵巢上皮性肿瘤的表达及临床意义。方法:应用免疫组化SP法,检测NF-κB/p65和VEGF在10例正常卵巢组织,20例卵巢良性上皮性肿瘤,10例卵巢交界性上皮性肿瘤,60例卵巢上皮性癌中的表达。结果:NF-κB/p65和VEGF在卵巢上皮性癌中的表达率均高于卵巢交界性上皮性肿瘤、卵巢良性上皮性肿瘤的表达率,差异有统计学意义(P<0.05)。卵巢上皮性癌中NF-κB/p65和VEGF的阳性表达率,中低分化组高于高分化组,有淋巴结转移组高于无淋巴结转移组,差异均有统计学意义(P<0.05);Ⅲ～Ⅳ期的表达率显著高于Ⅰ～Ⅱ期,差异有显著统计学意义(P<0.01)。卵巢上皮性癌患者腹水量>500m l组中VEGF表达率显著高于腹水量<500m l组(P<0.01),NF-κB/p65在腹水量>500m l组和腹水量≤500m l组中的表达率差异无统计学意义(P>0.05);VEGF与NF-κB/p65在卵巢肿瘤组织中的表达强度呈正相关(r=0.279,P<0.01)。结论:NF-κB/p65及VEGF与卵巢上皮性癌的发生发展有关,与卵巢上皮性癌病理分级、临床分期、淋巴结转移有关,VEGF与腹水形成有关;VEGF可作为判断预后的候选指标;NF-κB/p65对VEGF有调控作用。     

c-kit基因及其靶体SCF在卵巢上皮性肿瘤中的表达

目的:研究c-kit基因及其靶体干细胞因子(stem cell factor,SCF)在卵巢上皮性肿瘤的表达及临床意义,探讨其在卵巢上皮性癌发生发展中的可能作用。方法:免疫组化SP法测定10例正常卵巢组织,20例卵巢良性上皮性肿瘤,16例卵巢交界性上皮性肿瘤,58例卵巢上皮性癌标本中c-kit、SCF蛋白的表达。结果:(1)卵巢上皮性癌中c-kit蛋白阳性表达率为63.79%,明显高于正常卵巢组织(0%)及卵巢良性上皮性肿瘤(10.00%),差异有显著性(P<0.01);卵巢交界性上皮性肿瘤中c-kit阳性表达率为43.75%(7/16),也高于正常卵巢组织及卵巢良性上皮性肿瘤,差异有显著性(P<0.05);(2)卵巢上皮性癌中,低分化组的c-kit蛋白阳性表达率高于高、中分化组(P<0.05),c-kit蛋白的阳性表达率随FIGO分期的进展及淋巴结转移而升高(P<0.05);(3)c-kit阳性患者的预后比c-kit阴性患者差(P<0.05);(4)SCF在正常卵巢上皮、卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤、卵巢上皮性癌中的阳性表达率分别为30.00%、35.00%、62.50%和74.14%,卵巢上皮性癌的阳性表达率显著高于正常卵巢组织及卵巢良性上皮性肿瘤(均P<0.01)。卵巢癌低分化组SCF的阳性表达率显著高于高、中分化组(P<0.05)。且随FIGO分期的进展及淋巴结转移而升高(P<0.05);(5)c-kit与SCF表达具有明显相关性(r=0.302,P<0.05)。结论:(1)c-kit、SCF表达异常可能在卵巢上皮性癌的发生发展中起重要作用;(2)c-kit、SCF在卵巢上皮性癌中的表达具有相关性,SCF作为c-kit的配体,可促使c-kit活化,两者具有协同作用(3)c-kit蛋白表达与卵巢上皮性癌患者的预后有关,可作为判断卵巢上皮性癌患者预后的指标之一。     

卵巢上皮性肿瘤的临床病理特征及其细胞周期素D1和p53蛋白表达的研究

目的研究卵巢上皮性癌（卵巢癌）和交界性上皮性肿瘤的临床病理特征及其细胞周期素D1（cyclin D1）和p53蛋白表达的情况,探讨卵巢癌和交界性上皮性肿瘤在发病机制上的联系。方法分析45例卵巢癌（卵巢癌组）和54例卵巢交界性上皮性肿瘤（交界性肿瘤组）的临床病理资料,采用免疫组化法检测两组组织中cyclin D1、p53蛋白的表达情况,并分析其与临床病理特征的相关性。结果（1）临床病理特征：①年龄：交界性肿瘤组平均年龄为42．5岁（14～82岁）,中位数年龄41岁;卵巢癌组平均年龄为53．5岁（26～80岁）,中位数年龄51岁。②分期：按国际妇产科联盟（FIGO）分期标准,交界性肿瘤组Ⅰ期48例、Ⅱ期3例、Ⅲ期3例;卵巢癌组Ⅰ期6例、Ⅱ期8例、Ⅲ期26例、Ⅳ期5例。③病理类型：交界性肿瘤组以黏液型为主[占56％（30／54）],其次为浆液型[其中普通型11例,微乳头型5例;占30％（16／54）];卵巢癌组以浆液型（其中低度恶性19例,高度恶性3例）为主[占49％（22／45）]。④病理分化程度：卵巢癌组高分化5例,中分化17例,低分化或未分化23例。⑤预后：交界性肿瘤组5年生存率为98％,卵巢癌组为51％,两组比较,差异有统计学意义（P=0．000）。（2）cyclin D1和p53蛋白的表达及其与卵巢癌和交界性肿瘤临床病理特征的相关性：卵巢癌组cyclin D1和p53蛋白的阳性表达率分别为31％（14／45）和56％（25／45）,p53蛋白表达强度与病理分化程度呈正相关（r=0．320,P=0．032）;交界性肿瘤组cyclin D1和p53蛋白的阳性表达率分别为69％（37／54）和6％（3／54）。其中,普通型浆液性交界性肿瘤与高度恶性浆液性癌比较（两者cyclin D1蛋白阳性表达率分别为91％和26％,p53蛋白分别为0和58％）,差异有统计学意义（P〈O．01）;而微乳头型浆液性交界性肿瘤与低度恶性浆液癌比较（两者cyclin D1蛋白阳性表达率分别为3／5和2／3,p53蛋白分别为1／5和1／3）,差异则无统计学意义（P〉0．05）。结论cyclin D1蛋白的过度表达常见于卵巢浆液性交界性肿瘤及低度恶性浆液性癌组织中,而p53蛋白的过度表达更多见于高度恶性浆液性癌组织中。卵巢浆液性交界性肿瘤与高度恶性浆液性癌具有不同的发病机制,而微乳头型浆液性交界性肿瘤与低度恶性浆液性癌的关系可能更为密切。     

NF-кB/p65和VEGF在卵巢上皮性肿瘤的表达及临床意义

目的:研究NF-кB/p65和VEGF在卵巢上皮性肿瘤的表达及临床意义.方法:应用免疫组化SP法,检测NF-кB/p65和VEGF在10例正常卵巢组织,20例卵巢良性上皮性肿瘤,10例卵巢交界性上皮性肿瘤,60例卵巢上皮性癌中的表达.结果:NF-кB/p65和VEGF在卵巢上皮性癌中的表达率均高于卵巢交界性上皮性肿瘤、卵巢良性上皮性肿瘤的表达率,差异有统计学意义(P＜0.05).卵巢上皮性癌中NF-кB/p65和VEGF的阳性表达率,中低分化组高于高分化组,有淋巴结转移组高于无淋巴结转移组,差异均有统计学意义(P＜0.05);Ⅲ～Ⅳ期的表达率显著高于Ⅰ～Ⅱ期,差异有显著统计学意义(P＜0.01).卵巢上皮性癌患者腹水量＞500ml组中VEGF表达率显著高于腹水量＜500ml组(P＜0.01),NF-кB/p65在腹水量＞500ml组和腹水量≤500ml组中的表达率差异无统计学意义(P＞0.05);VEGF与NF-кB/p65在卵巢肿瘤组织中的表达强度呈正相关(r=0.279,P＜0.01).结论:NF-кB/p65及VEGF与卵巢上皮性癌的发生发展有关,与卵巢上皮性癌病理分级、临床分期、淋巴结转移有关,VEGF与腹水形成有关;VEGF可作为判断预后的候选指标;NF-кB/p65对VEGF有调控作用.     

八聚体结合转录因子4与蛋白激酶B1基因在卵巢浆液性肿瘤组织表达及耐药相关性研究

目的 研究八聚体结合转录因子4（OCT4）和蛋白激酶B1（AKT1）基因在卵巢浆液性肿瘤组织中的表达,探讨两者之间相关性及在化疗耐药中发挥的作用。 方法 全部病例来自中国医科大学附属盛京医院2004年1月至2010年10月。采用免疫组织化学SP法对67例卵巢浆液性腺癌（化疗耐药30例,化疗敏感37例）、10例卵巢交界性浆液性囊腺瘤、10例卵巢良性浆液性囊腺瘤和10例正常卵巢组织中OCT4和AKT1的表达情况进行检测。 结果 OCT4的阳性表达率在卵巢浆液性腺癌、卵巢交界性浆液性囊腺瘤、卵巢良性浆液性囊腺瘤和正常卵巢组织中依次降低,差异具有统计学意义（P=0.002）;在耐药组和敏感组的阳性表达率分别为83.33%和45.95%,差异有统计学意义（P=0.002）。AKT1蛋白在正常组、良性组、交界性组和恶性组的阳性表达率分别为0、40.00%、70.00%、62.69%,差异具有统计学意义（P=0.001）;在耐药组和敏感组的阳性表达率分别为76.67%和51.35%, 两组比较,差异有统计学意义（P=0.033）。OCT4蛋白与卵巢浆液性癌临床病理因素无关,AKT1蛋白与卵巢浆液性癌的临床分期呈正相关（P<0.05）。OCT4与AKT1蛋白在耐药组中呈正相关（r=0.388,P=0.034）;在敏感组无明显相关性（r=0.246,P=0.142）。     

人抗原RmRNA与蛋白和环氧合酶-2蛋白在卵巢浆液性肿瘤组织中的表达及其意义

目的 探讨人抗原R（human antigen R,HuR）mRNA与蛋白和环氧合酶-2（COX-2）蛋白在卵巢浆液性肿瘤组织中的表达及其与卵巢浆液性癌临床病理生物学特征的关系。方法 采用RT-PCR技术、免疫组化方法分别检测中国医科大学附属盛京医院2006年1月至2008年2月收集的31例卵巢浆液性癌组织标本、22例卵巢浆液性良性瘤组织标本中HuR mRNA与蛋白和COX-2蛋白的表达,并以8例正常卵巢组织作为对照组。结果 （1）HuR mRNA在卵巢浆液性癌中表达明显高于卵巢浆液性良性瘤和正常卵巢组织（P<0.05）。HuR mRNA 的表达与卵巢浆液性癌细胞分化有关（P<0.05）,与手术病理分期、淋巴结转移无关（P>0.05）。（2）HuR蛋白相对含量和胞浆表达阳性率在卵巢浆液性癌中的表达显著高于卵巢浆液性良性瘤和正常卵巢组织（P<0.05）。HuR蛋白相对含量和胞浆表达阳性率与卵巢浆液性癌细胞分化有关（P<0.05）,与手术病理分期、淋巴结转移无关（P>0.05）。（3）COX-2蛋白相对含量与卵巢浆液性癌手术病理分期有关（P<0.05）,与细胞分化、淋巴结转移无关（P>0.05）。依据31例卵巢浆液性癌中免疫组化结果半定量分析,经Spearman等级相关分析发现HuR与COX-2之间呈正相关（r=0.680,P=0.000）。结论 卵巢浆液性肿瘤的发展与胞浆中HuR的过表达有一定相关性,HuR与COX-2蛋白在卵巢浆液性癌中的表达呈正相关。     

Survivin、caspase-3及PCNA在卵巢上皮性肿瘤中表达的临床意义

目的 探讨凋亡调控因子Survivin、半胱氨酸天门冬氨酸蛋白酶-3(caspase-3)及细胞增殖标记指数(PCNA)在卵巢上皮性肿瘤中表达的临床意义.方法 采用免疫组织化学技术,检测2006年1月至2006年12月哈尔滨医科大学第一临床医学院收治的40例卵巢上皮性癌、10例交界性卵巢上皮性肿瘤组织及10例卵巢良性上皮性肿瘤中Survivin、caspase-3和PCNA的蛋白表达,并结合临床病理特征进行分析.结果 Survivin、caspase-3在卵巢上皮性肿瘤中表达呈负相关;Survivin和PCNA的蛋白表达呈正相关;Survivin在卵巢上皮性癌中表达率72.5%(29/40),且表达水平高于卵巢良性上皮性肿瘤(0)和交界性卵巢上皮性肿瘤(40%)(P＜0.05).caspase-3在卵巢上皮性癌中表达率0.5%(2/40),且表达水平远远低于卵巢良性上皮性肿瘤和交界性卵巢上皮性肿瘤(P＜0.01).结论 Survivin可能抑制caspase-3在卵巢癌中表达,导致卵巢癌细胞增殖,凋亡受阻,肿瘤形成;Survivin基因的表达可能发生在卵巢癌恶性转化的早期;Survivin的表达与瘤细胞分化、增殖密切相关,并且其高表达可能会作为预后不良的标志;caspase-3在卵巢癌中极低表达,有望成为卵巢癌良恶鉴别新的指标.     

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。     

葡萄糖转运蛋白1在卵巢上皮性癌组织中的表达及其与碱性成纤维生长因子、增殖细胞核抗原表达的关系

目的探讨卵巢上皮性癌组织中葡萄糖转运蛋白1(GLUT1 )的表达及其与碱性成纤维生长因子(bFGF)、增殖细胞核抗原(PCNA)表达的关系。方法采用免疫组化链霉菌抗生物素蛋白过氧化物酶连接法(SP法)检测6例正常卵巢、20例卵巢良性肿瘤、7例卵巢交界性肿瘤和44例卵巢上皮性癌组织中GLUT1、bFGF、PCNA的表达,并对GLUT1 与bFGF、PCNA表达的关系进行了相关性分析。结果GLUT1 在正常卵巢、卵巢良性肿瘤组织中不表达,而在卵巢交界性肿瘤及卵巢上皮性癌组织中阳性表达率分别为6 /7、91% (40 /44),卵巢上皮性癌组织中GLUT1 的阳性表达率明显高于卵巢交界性肿瘤组织(P<0 05)。卵巢上皮性癌组织中GLUT1 的阳性表达率与病理分级、手术病理分期、远处转移、淋巴结转移均呈明显正相关(P<0 01),而与病理类型无关(P=0 513)。在卵巢上皮性癌组织中,bFGF阳性表达25例,其中3例GLUT1 染色强度为( ++)、22例( +++);阴性表达19例,其中4例GLUT1 染色强度为( -)、4例( +)、8例( ++)、3例( +++),bFGF阳性表达者GLUT1 染色强度高于bFGF阴性表达者,差异有统计学意义(P<0 01)。GLUT1 染色强度与PCNA标记指数相关,GLUT1 染色强度为( +)、( ++)、( +++)的卵巢上皮性癌组织的PCNA标记指数分别为0 40、0 43、0 69,GLUT1 染色强度为( +++)的卵巢     

Foxp3在卵巢上皮性癌组织中的表达及其与预后相关性的研究

目的:探讨Foxp3在卵巢上皮性癌组织中的表达及其与预后的相关性。方法:选取2003年1月至2007年12月在上海交通大学医学院附属仁济医院诊治的卵巢上皮性癌患者的组织标本,用免疫组化法测定Foxp3在卵巢良性上皮性肿瘤、交界性上皮性肿瘤和恶性上皮性肿瘤组织中的表达,并比较卵巢上皮性癌相关的临床指标及病理学因素。结果:Foxp3在卵巢上皮性癌中阳性表达率为56.7%(17/30),显著高于卵巢良性上皮性肿瘤(0%,0/10)和交界性卵巢肿瘤(20%,2/10)(P=0.001,P<0.05)。Foxp3的表达与组织学分级显著相关(P=0.004)。Foxp3(+)与Foxp3(-)患者的生存曲线差异接近统计学差异水平(P=0.057)。结论:Foxp3表达升高与卵巢癌的预后不良存在相关趋势。     

B7-H4 overexpression in ovarian tumors

OBJECTIVES: Despite great advances in therapeutic management, the mortality rate for ovarian cancer has remained relatively stable over the past 50 years. This study was designed to evaluate the expression of B7-H4 protein, recently identified as a potential molecular marker of breast and ovarian cancer by quantitative PCR analysis, in benign tumors, tumors of low malignant potential and malignant tumors of the ovary. METHODS: Archival formalin-fixed tissue blocks from serous, mucinous, endometrioid and clear cell ovarian tumors were evaluated by immunohistochemistry for the distribution of B7-H4 expression, and staining intensity was measured by automated image analysis. Univariate analyses were used to test for statistically significant relationships. RESULTS: B7-H4 cytoplasmic and membranous expression was detected in all primary serous (n = 32), endometrioid (n = 12), and clear cell carcinomas (n = 15), and in all metastatic serous (n = 23) and endometrioid (n = 7) ovarian carcinomas. By contrast, focal B7-H4 expression was detected in only 1/11 mucinous carcinomas. The proportion of positive cells and median staining intensity was greater in serous carcinomas than in serous cystadenomas or serous tumors of low malignant potential, and the differences were statistically significant (P < 0.0001 and P = 0.034, respectively). The median staining intensity was also significantly greater in endometrioid carcinomas than in endometriosis (P = 0.005). CONCLUSIONS: The consistent overexpression of B7-H4 in serous, endometrioid and clear cell ovarian carcinomas and the relative absence of expression in most normal somatic tissues indicates that B7-H4 should be further investigated as a potential diagnostic marker or therapeutic target for ovarian cancer.     

Wnt信号通路成分β-catenin和APC在卵巢肿瘤中的表达及意义

目的:探讨Wnt信号通路成分β-catenin和APC基因在上皮性卵巢癌的表达及意义。方法:应用免疫组织化学染色SABC法检测49例卵巢癌(24例浆液性囊腺癌、15例黏液性囊腺癌、10例子宫内膜样癌),10例交界性卵巢肿瘤及16例良性卵巢肿瘤中β-catenin、APC基因的表达,分析其相关性。结果:卵巢癌中β-catenin的异常表达率明显高于卵巢交界性肿瘤和卵巢良性肿瘤,差异有统计学意义(P0.05)。卵巢癌中APC基因的阴性表达率明显高于卵巢良性肿瘤,差异有统计学意义(P0.05),而与卵巢交界性肿瘤无显著差异(P0.05)。卵巢癌中APC基因的阴性表达与β-catenin的异常表达无相关性(r=0.0429,P0.05)。2例卵巢子宫内膜样癌中可见β-catenin胞核表达,但不伴有APC基因的阴性表达。结论:卵巢癌中Wnt信号通路中的成分发生变化,但其激活机制可能有别于Wnt信号通路的传统激活机制,可能在卵巢子宫内膜癌的发生中发挥作用。     

p63 expression in epithelial ovarian tumors

Ovarian cancer is a highly lethal disease and its underlying biology is poorly understood. The p63 is a homologue gene of the tumor suppressor p53. p63 appears to be important for the development and differentiation of reproductive epithelium and interacts with p53 in human tumorigenesis. This study presents the immunoexpression of the p63 in benign and malignant epithelial ovarian tumors. We evaluated the p63 immunoexpression in 91 ovarian benign cystadenomas (29 mucinous and 62 serous) and in 29 ovarian malignant tumors (3 mucinous borderline, 3 serous borderline, 17 serous carcinomas, 2 endometrioid, 2 undifferentiated, 1 mucinous, and 1 clear-cell carcinoma) using a monoclonal antibody clone 4A4 (1:200), which recognizes all p63 variants. The tumors were considered p63 positive if 5% or more cells presented nuclear immunostaining. We observed 85.7% of positivity in benign tumors, 50% in borderline tumors, and 8.7% in invasive ovarian cancer (P < .0001). The benign serous cystadenomas were positive in 91.9% of cases and benign mucinous cystadenomas in 72.4% (P= .02). These data suggests an important role of p63 in the control of ovarian epithelium behavior. The p63 may be involved in the development of benign and malignant epithelial ovarian tumors.     

Subclassification of ovarian surface epithelial tumors based on correlation of histologic and molecular pathologic data.

Surface epithelial tumors are a large and heterogeneous group of neoplasms that are subclassified based on cell type and malignant potential. The objective of this review is to examine the correlations between recent molecular pathology data and the traditional histopathologic classification of surface epithelial tumors. By doing so, 6 distinct subsets of ovarian epithelial neoplasia can be identified with potential treatment implications 1. high-grade serous, high-grade endometrioid, and undifferentiated carcinomas; 2. low-grade serous carcinomas and serous borderline tumors; 3. mucinous carcinomas and mucinous borderline tumors of intestinal type; 4. low-grade endometrioid carcinomas and endometrioid borderline tumors; 5. clear cell carcinomas; and 6. transitional cell carcinomas.     

Oviductal glycoprotein, a new differentiation-based indicator present in early ovarian epithelial neoplasia and cortical inclusion cysts

OBJECTIVE: With neoplastic progression, the precursor of epithelial ovarian cancers, the ovarian surface epithelium (OSE), undergoes Mullerian differentiation, usually of the oviductal type. The aim of this study was to examine the expression of oviduct-specific glycoprotein (OGP), a marker of normal oviductal epithelium, for use as a diagnostic or prognostic marker for ovarian cancer. METHODS AND MATERIALS: Immunohistochemical analysis for OGP was performed on 389 ovarian tumors and 19 normal ovaries, as well as 433 cases representing 45 normal tissues and 51 benign and malignant tumor types from 37 different tissues. RESULTS: OGP was absent in OSE but present in 28 of 31 epithelial inclusion cysts, 13 of 14 (93%) serous cystadenomas, and 46 of 65 (71%) serous borderline tumors. Of 183 serous adenocarcinomas, 26 (14%) were positive for OGP, including 5 of 8 (63%) grade I, 7 of 41 (17%) grade II, and 14 of 134 (10%) grade III carcinomas. OGP was found in 7 of 14 (50%) borderline and 9 of 15 (60%) malignant mucinous ovarian tumors and in 10 of 39 (26%) endometrioid adenocarcinomas. The localization of OGP in the lumen of glandular structures suggested that it was secreted. OGP was absent in 41 of 45 normal tissues and positive in oviduct and, weakly, in salivary gland, duodenum, and ileum. Forty-six types of nongynecologic tumors were negative, as were gynecologic neoplasms except for 2 of 47 cervical and 3 of 56 endometrial carcinomas. CONCLUSION: OGP is a new tubal differentiation marker which characterizes benign and borderline serous neoplasms and may indicate early events in ovarian carcinogenesis.     

膜联蛋白A8在卵巢上皮性浆液性肿瘤中的表达及临床意义

目的:检测膜联蛋白A8(Annexin A8,ANXA8)在卵巢组织中的表达,探讨其表达与卵巢上皮性浆液性恶性肿瘤患者临床病理参数及预后的相关性。方法:采用免疫组织化学法检测75例卵巢组织(正常卵巢组织组11例、卵巢浆液性良性肿瘤组13例、卵巢浆液性交界性肿瘤组17例、卵巢浆液性恶性肿瘤组34例)中ANXA8的表达,分析其与卵巢癌患者临床病理参数及疾病预后的关系。结果:ANXA8主要定位于细胞膜及细胞质,ANXA8在卵巢浆液性恶性肿瘤组中的高表达率(23/34,67.65%)明显高于正常卵巢组织组(1/11,9.09%)、卵巢浆液性良性肿瘤组(3/13,23.08%)及卵巢浆液性交界性肿瘤组(5/17,29.41%),差异有统计学意义(P分别为0.001、0.006、0.010)。在34例卵巢浆液性恶性肿瘤患者中,FIGOⅢ~Ⅳ期患者的ANXA8的高表达率(21/24,87.5%)明显高于FIGOⅠ~Ⅱ期患者(2/10,20.0%),差异具有统计学意义(P<0.001);盆腹腔残余病灶直径>1 cm患者的ANXA8高表达率(15/17,88.2%)明显高于残余病灶≤1 cm患者(8/17,41.2%),差异有统计学意义(P=0.010)。Kaplan-Meier生存分析表明,FIGO分期、淋巴转移、残余病灶、ANXA8的表达都是影响总生存期(OS)的重要因素(均P<0.05)。Cox多元回归分析表明ANXA8的高表达是影响卵巢浆液性恶性肿瘤患者预后的独立危险因素(P=0.019,HR=11.465,95%CI:1.498~87.757)。结论:ANXA8在卵巢上皮性浆液性恶性肿瘤组织中表达升高,且与卵巢癌不良预后有关,可用于临床监测卵巢上皮性浆液性恶性肿瘤患者病情变化。     

Loss of heterozygosity at the RB-1 locus and pRB immunostaining in epithelial ovarian tumors: a molecular, immunohistochemical, and clinicopathologic study.

Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia. The frequency of loss of heterozygosity (LOH) at the RB-1 locus on chromosome 13q14 was studied in a series of 51 epithelial ovarian tumors (10 benign, 7 borderline, and 34 malignant). LOH was scored by the absence or reduction of the signal to < 50% of one of the alleles in tumor DNA compared with normal DNA. LOH results were correlated with retinoblastoma protein (pRB) immunostaining. LOH at the RB-1 locus was observed in 9 tumors (17.6%), specifically in 1 of 7 borderline tumors and 8 of 34 ovarian carcinomas (23.5%). Among the malignant tumors, LOH occurred more frequently in carcinomas with serous differentiation (7/23; 30%). A heterogeneous (10% to 70% cells) or diffuse (> 70% cells) pRB immunostaining was less frequent in benign (1/10; 10%) and borderline (2/7; 28%) tumors than in ovarian carcinomas (15/34; 44%), an observation that correlated with the higher proliferative index in carcinomas than in benign and borderline tumors. However, lack or only focal (< 10% cells) pRB immunostaining occurred in the vast majority of tumors with LOH at the RB-1 locus (7/9; 77%), a finding that may suggest a tumor suppressor role for RB-1 in these tumors. The results suggest that RB-1 may play a role in a subset of ovarian carcinomas, particularly those exhibiting serous differentiation.