MMPs和TIMPs在卵巢上皮性肿瘤中表达的分析

目的　体内组织重建和生理过程中基质金属蛋白酶 (MMPs)和特异性抑制剂 (TIMPs)保持着动态平衡 ,不同的TIMP对不同的MMP具有不同的亲和性 ,本课题旨在研究MMP2、MMP9、TIMP1和TIMP2在卵巢上皮性肿瘤中的表达及其作用。方法　收集 1 996年 5月～ 2 0 0 1年 5月在浙江大学医学院附属妇产科医院行手术切除 ,并用福尔马林固定、石蜡包埋的 1 32例病例 ,运用免疫组织化学染色法检测。结果　MMP2、MMP9、TIMP1和TIMP2均表达于细胞胞浆内 ,均随着上皮性卵巢肿瘤恶性程度的增加 ,表达增强 ;在有淋巴结转移的患者中表达明显高于无淋巴结转移者 ;且MMP9 TIMP1、MMP2 TIMP2比例在恶性卵巢上皮性肿瘤中明显增高 ;相关性分析表明MMP2和TIMP2、MMP9和TIMP1间存在相关性 (P <0 0 0 0 1 )。结论　MMP2、MMP9、TIMP1和TIMP2与卵巢上皮性肿瘤的演化、侵袭过程关系密切     

MMP-9及TIMP-1与胎膜早破关系的研究

目的 :研究胎膜早破 (PROM)孕妇羊水、血清中基质金属蛋白酶 9(MMP 9)、金属蛋白酶组织抑制剂 1(TIMP 1)的含量及在胎膜中的表达 ,探讨其与PROM的关系。方法 :选择临产前足月剖宫产分娩的胎膜早破者 2 5例 (PROM组 )和正常未破膜者 2 0例 (对照组 ) ,用双抗体夹心ELISA法测定羊水、血清中MMP 9、TIMP 1的含量 ,并用免疫组化SABC法检测胎膜中MMP 9及TIMP 1的表达。结果 :①PROM组和对照组羊水中MMP 9含量分别为 (887.2 4± 36 3.2 5 )与(6 6 6 .15± 2 39.5 8)ng/ml,差异有显著性 (P <0 .0 5 ) ;两组血清中MMP 9含量分别为 (38.72± 2 3.4 8)与 (17.4 5± 10 .77)ng/ml,差异有非常显著性 (P <0 .0 0 1) ;两组羊水与血清中TIMP 1含量差异无显著性 (P >0 .0 5 )。②PROM组血清与羊水中MMP 9、TIMP 1的含量无相关性 (r分别为 0 .133与 0 .10 3,P >0 .0 5 )。③PROM组和对照组胎膜MMP 9的阳性表达分别为 10 0 %、85 % ,差异有非常显著性 (P <0 .0 0 1)。结论 :胎膜早破孕妇羊水、血清中MMP 9含量明显升高 ,且MMP 9在胎膜中高表达 ,可能是胎膜早破发生的原因之一     

基质金属蛋白酶-9及其组织抑制剂TIMP-3在子宫内膜异位症的表达

目的 :探讨基质金属蛋白酶 9(MMP 9)及其抑制剂TIMP 3在子宫内膜异位症发生发展中的作用。方法 :采用免疫组化链霉菌抗生物素蛋白 过氧化物酶染色法 (SP法 )检测 4 3例子宫内膜异位症的异位内膜和在位内膜中MMP 9、TIMP 3的表达 ,以 19例正常子宫内膜为对照组 ,并用银染法观察腺上皮基底膜的完整性。结果 :在异位内膜组织的腺上皮细胞MMP 9呈高表达状态 ,与子宫内膜异位症在位内膜和正常子宫内膜相比 ,差异有高度显著性 (P <0 .0 1)。子宫内膜异位症的在位内膜和异位内膜TIMP 3均呈低表达 ,与正常内膜相比 ,差异有高度显著性 (P <0 .0 1) ,异位内膜较在位内膜TIMP 3的表达降低 ,差异有显著性 (P <0 .0 5 )。子宫内膜腺上皮的基底膜银染结果显示 :MMP 9与TIMP 3的染色强度比值与基底膜的阳性率呈负相关 (P <0 .0 1)。MMP 9、TIMP 3的表达强度与子宫内膜异位症的严重程度无显著相关性。结论 :异位内膜组织中MMP 9过度表达 ,而TIMP 3的表达下降 ,导致MMP 9/TIMP 3的比例增高 ,使子宫内膜异位症患者的异位内膜更具侵袭性 ,在子宫内膜异位症的发生发展中起重要作用     

MMP-2、TIMP-2、Ki-67在库肯勃氏瘤中的表达及意义

目的 :探讨MMP 2、TIMP 2、Ki 67表达与库肯勃氏瘤病理生物学行为的关系。方法 :采用免疫组化SP法对 32例库肯勃氏瘤组织和 10例正常卵巢组织进行MMP 2、TIMP 2和Ki 67表达的检测。结果 :MMP 2、TIMP 2、Ki 67在库肯勃氏瘤组织中的表达量显著高于正常卵巢组织 (P <0 .0 1)。有合并转移的库肯勃氏瘤中MMP 2、Ki 67高于无合并转移者 (P <0 .0 5 ) ,TIMP 2低于无合并转移者 (P <0 .0 5 )。MMP 2、Ki 67与术后生存时间呈负相关 (P <0 .0 1) ,TIMP 2与术后生存时间呈正相关 (P <0 .0 1)。结论 :MMP 2、TIMP 2、Ki 67在库肯勃氏瘤发生、发展中起重要作用 ,可作为判断卵巢转移癌恶性程度、临床分期和评估预后的临床参考指标     

基质金属蛋白酶2、9及其特异性组织抑制剂在自发性胎膜早破发病中的作用

目的　探讨基质金属蛋白酶 (MMP) 2、9及其特异性组织抑制剂 (TIMP)在自发性胎膜早破发病中的作用。方法　采用RT PCR方法对 8例自发性胎膜早破患者 (胎膜早破组 )、8例正常阴道分娩产妇 (阴道分娩组 )以及 8例择期剖宫产产妇 (剖宫产组 )的胎膜组织中MMP 2、MMP 9和TIMP 2、TIMP 1mRNA的表达进行检测。结果　 (1)MMP 2 :胎膜早破组为 0 84 9± 0 0 37,阴道分娩组为 0 32 7± 0 0 2 3,剖宫产组为 0 30 7± 0 0 2 8。胎膜早破组MMP 2表达水平明显高于阴道分娩组和剖宫产组 ,两组比较 ,差异有统计学意义 (P <0 0 5 ) ;阴道分娩组MMP 2表达水平与剖宫产组比较 ,差异均无统计学意义 (P >0 0 5 )。 (2 )MMP 9:胎膜早破组为 0 0 2 6± 0 0 0 4 ,阴道分娩组为 0 0 0 8± 0 0 0 1,剖宫产组无表达。胎膜早破组MMP 9表达水平明显高于阴道分娩组 ,两者比较 ,差异有统计学意义 (P <0 0 5 )。 (3)TIMP 2 :胎膜早破组为 0 4 2 0± 0 12 2 ,阴道分娩组为 0 730± 0 14 8,剖宫产组为 0 885± 0 0 6 5。胎膜早破组TIMP 2表达水平明显低于阴道分娩组和剖宫产组 ,两者比较 ,差异有统计学意义 (P <0 0 5 ) ;阴道分娩组TIMP 2表达水平明显低于剖宫产组 ,两组比较 ,差异有统计学意义 (P <0 0 5 )。 (4)TI     

原因不明性不孕患者子宫内膜基质金属蛋白酶-9 mRNA的表达及其性激素调节

目的　检测基质金属蛋白酶 9(MMP 9)及其抑制物 1 (TIMP 1 )mRNA在原因不明性不孕患者黄体中期子宫内膜中的表达 ,及与性激素的相关性。方法　采用原位杂交、逆转录聚合酶链反应(RT PCR)技术 ,对 38例原因不明不孕患者 (研究组 )和 2 0例正常生育期妇女志愿者或男方因素不孕患者 (对组照 )的黄体中期子宫内膜行MMP 9、TIMP 1mRNA检测 ,同期放射免疫法测定雌二醇 (E2 )、孕酮 (P)水平。结果　子宫内膜腺上皮、间质细胞胞浆、胞核均有MMP 9、TIMP 1mRNA的表达 ,研究组较对照组表达少 ,研究组黄体中期子宫内膜MMP 9mRNA表达水平为 0 .42± 0 .1 9,显著低于对照组的 0 .57± 0 .1 9(P <0 .0 5) ;研究组TIMP 1mRNA表达水平为 0 .59± 0 .1 9,显著低于对照组的 0 81± 0 .2 0 (P <0 .0 1 )。研究组黄体中期血清P水平为 (34± 1 5)nmol/L ,显著低于对照组的 (53± 1 7)nmol/L(P<0 .0 1 ) ,而血清E2 水平与对照组比较 ,差异无显著性 (P >0 .0 5)。对照组P水平与MMP 9mRNA表达呈正相关 (r=0 .72 2 ,P <0 .0 1 ) ,而研究组无相关性 (P >0 .0 5) ;两组P水平与TIMP 1mRNA ,E2 与MMP 9、TIMP 1mRNA均无相关性 (P >0 .0 5)。结论　原因不明不孕患者黄体中期P水平影响MMP 9、TIMP 1mRNA的表达并致活性下降 ,可能与不孕     

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。     

基质金属蛋白酶和卵巢肿瘤的关系

目的　研究基质金属蛋白酶 (MMP) - 2 ,- 9在卵巢上皮恶性和良性肿瘤的血管内皮和腺上皮的表达。方法　选取手术病例 18例 ,分为卵巢上皮恶性肿瘤 11例和卵巢良性肿瘤 7例 ,两组均经病理检查确诊。用免疫组化染色 ,图片经计算机扫描分析 ,数据以X±S表示 ,进行t检验。结果　①卵巢上皮恶性和良性肿瘤血管内皮MMP - 2蛋白的表达分别为 1 0 5 6± 0 0 5 7和 0 85 5± 0 0 86 ,(P <0 0 1) ;腺上皮MMP - 2蛋白的表达为 1 0 84± 0 0 6 1和 0 82 0± 0 0 32 ,(P <0 0 1)。②卵巢上皮恶性和良性肿瘤血管内皮MMP - 9蛋白的表达分别为 1 0 0 6± 0 0 5 1和 0 935± 0 0 5 5 ,(P <0 0 1) ;腺上皮MMP - 9蛋白的表达分别为 1 4 39± 0 0 15和 0 92 8± 0 0 4 2 ,(P <0 0 1)。③卵巢上皮恶性肿瘤血管内皮的MMP - 2的蛋白表达高于MMP - 9(P <0 0 1) ;腺上皮的MMP - 2低于MMP - 9(P <0 0 1)。结论　MMP - 2和MMP - 9蛋白在卵巢上皮恶性肿瘤的血管内皮和腺上皮表达均高于良性肿瘤。MMP - 2 ,- 9蛋白在卵巢上皮恶性肿瘤血管内皮和腺上皮的表达差异 ,提示MMP - 2 ,- 9在卵巢上皮恶性肿瘤的血管发生及肿瘤转移中发挥不同的作用     

层粘连蛋白、基质金属蛋白酶-9在卵巢粘液性肿瘤中的表达及其意义

目的 :探讨层粘连蛋白 (LN)、基质金属蛋白酶 9(MMP 9)在卵巢粘液性肿瘤中的表达以及与临床病理因素和预后的关系。方法 :应用免疫组织化学方法检测 43例卵巢粘液性肿瘤LN、MMP 9的表达情况。结果 :LN、MMP 9的表达 ,在卵巢粘液性肿瘤从良性、交界性到恶性发展中 ,LN的表达级别和MMP 9的表达阳性率逐渐增高 ;LN的表达程度与卵巢粘液性囊腺癌的组织学分级有关 (P =0 0 0 0 ) ;MMP 9的表达与卵巢粘液性囊腺癌的组织学分级 (P =0 0 48)、FIGO分期 (P =0 0 47)、术后复发和死亡 (P =0 0 30 )有关。在卵巢粘液性囊腺癌中 ,LN的表达程度在MMP 9阳性组与MMP 9阴性组之间差异有显著性 (P =0 0 0 8) ,并呈正相关。结论 :LN、MMP 9在卵巢粘液性肿瘤的浸润转移中起重要作用 ,是卵巢粘液性肿瘤的恶性指标之一 ,可望作为交界性粘液性囊腺瘤及粘液性囊腺癌的诊断和分级的客观指标 ;MMP 9可协助临床估计预后。     

基质金属蛋白酶-9及基质金属蛋白酶组织抑制物-1表达失衡与宫颈癌局部肿瘤血管生成的关系

目的 :探讨基质金属蛋白酶 - 9(MMP 9)和基质金属蛋白酶组织抑制物 - 1(TIMP 1)在宫颈癌局部肿瘤血管生成中的作用。方法 :采用免疫组织化学SP法检测 75例早期宫颈癌 (ICC)、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮 (NCE)中MMP 9和TIMP 1的表达情况 ,并检测其中微血管密度 (MVD ,CD3 4 标记 )。结果 :从NCE组到CIN组再到ICC组 ,MMP 9的阳性表达率显著升高 (P <0 0 5 )而TIMP 1未见升高 (P >0 0 5 ) ,并且TIMP 1在ICC组的阳性表达率显著低于MMP 9(P <0 0 1)。MMP 9在ICC组中表达与MVD显著正相关 (r =0 2 87,P <0 0 5 ) ,而TIMP 1与MVD无显著相关性 (r=0 195 ,P >0 0 5 )。宫颈癌中MMP 9表达高于TIMP 1者 ,其MVD显著高于MMP 9表达低于TIMP 1者 (P <0 0 5 )。结论 :MMP 9和TIMP 1表达失衡可能在宫颈癌局部肿瘤血管生成中起重要作用 ,MMP 9表达增强而TIMP 1表达降低 ,其血管生成能力可能显著增强 ,但并非唯一决定因素。检测宫颈癌中MMP 9和TIMP 1表达对进一步了解宫颈癌局部血管生成情况有一定的应用价值。     

Differential expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 protein and mRNA in epithelial ovarian tumors

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) can degrade gelatin and type IV collagen and is known to play an important role in tumor cell invasion across the basement membrane. The tissue inhibitor of metalloproteinase-1 (TIMP-1) is able to prevent activation of pro-MMP-9 and forms a 1:1 complex with the active form of MMP-9. The aim of the present study was to investigate the expression of MMP-9 and TIMP-1 in benign, borderline, and invasive epithelial ovarian tumors. MATERIALS AND METHODS: A total of 90 patients with epithelial ovarian tumor were treated at the Brigham and Women's Hospital and were used as the study population. Immunohistochemistry and in situ hybridization were performed to detect protein and mRNA expression of MMP-9 and TIMP-1. RESULTS: In the 90 epithelial ovarian tumors tested, MMP-9 expression in tumor cells was found to be significantly enhanced in serous and mucinous ovarian carcinomas compared with benign and borderline tumors. We also observed the immunostaining of MMP-9 in stromal cells of benign, borderline, and invasive epithelial ovarian tumors. Moreover, the expression levels of TIMP-1 in tumor cells were significantly higher in borderline and invasive ovarian tumors than in benign tumors. CONCLUSION: Using an in situ hybridization technique, we disclosed a direct correlation between the presence of mRNA and protein expression for both MMP-9 and TIMP-1. The present data suggest that high levels of MMP-9 protein in invasive epithelial ovarian carcinoma are strongly associated with tumor cell invasion. Enhanced expression of TIMP-1 protein in borderline and invasive tumors indicates that endogenous TIMP-1 protein may play a paradoxical role in ovarian tumor progression.     

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。     

Expression of matrix metalloproteinases and related tissue inhibitors in the cyst fluids of ovarian mucinous neoplasms

OBJECTIVES AND METHODS: The growth of an ovarian cystic neoplasm often involves its invasion into and destruction of the extracellular matrix. We examined neoplastic cysts of ovarian mucinous tumors for the presence of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) using zymography (in situ zymography, gelatin zymography, and casein zymography) and enzyme-linked immunosorbent assay. RESULTS: Matriolytic activity was detected within the cystic contents and cytoplasm of the lining epithelial cells of the cyst by in situ zymography. This intracystic matriolytic activity was thought to originate mainly in the epithelial cells. The activated form of MMP-9 was seen in all carcinoma and borderline fluids and in 7 of 15 adenomas. The concentration of MMP-9 was higher in carcinoma fluids than in borderline and adenoma fluids (P < 0.05). TIMP-1, which specifically binds to MMP-9, was also higher in carcinoma and borderline fluids than in adenoma fluids (P < 0.05). MMP-2 activity was nearly ubiquitously present in all cyst fluids, irrespective of the fluid's histologic category. The amount of MMP-2 was highest in the carcinoma category, although not to a statistically significant degree. TIMP-2, a specific inhibitor for MMP-2, was significantly lower in the borderline category than in the adenoma category. The molar ratios of TIMP-1/MMP-9 (not significant) and TIMP-2/MMP-2 (P < 0.05) were higher in the adenoma category. Expressions of trypsin, MMP-7, and MMP-9 were generally higher in carcinoma and borderline fluids than in adenoma fluids. CONCLUSIONS: These observations indicate the importance of ovarian cystic fluids for analyzing tumor-associated matriolytic activities. The findings suggest that these matriolytic enzymes, together with the presence of their inhibitors, play an important role in the growth of ovarian mucinous tumors.     

卵巢上皮性肿瘤组织中KiSS-1、基质金属蛋白酶9和核因子κBp65蛋白的表达及其相关性

目的 探讨KiSS-1、基质金属蛋白酶9（MMP-9）、核因子κB（NF-κB）p65蛋白3者在卵巢上皮性肿瘤组织中的表达及其相关性。方法 采用免疫组化方法检测50份卵巢上皮性癌（卵巢癌）、20份卵巢交界性肿瘤、20份卵巢良性肿瘤和10份正常卵巢组织中KiSS-1、MMP-9、NF-κBp65蛋白的表达,并分析其临床意义及3者间的相关性。结果 KiSS-1蛋白在卵巢癌组织中的阳性表达率（80％）明显高于良性肿瘤组织及正常卵巢组织（分别为35％、10％;P〈0．05）;在卵巢交界性肿瘤组织中阳性表达率（65％）明显高于正常卵巢组织（P〈0．05）。在卵巢癌组织中,KiSS-1蛋白阳性表达率与淋巴结转移有关（P〈0．05）,与手术病理分期、病理类型及病理分级均无关（P〉0．05）;MMP-9蛋白阳性表达率与手术病理分期及淋巴结转移有关（P〈0．05）,而与病理类型及病理分级均无关（P〉0．05）;NF-KBp65蛋白阳性表达率与手术病理分期、病理分级及淋巴结转移有关（P〈0．05）,而与病理类型无关（P〉0．05）。在卵巢癌组织中,KiSS-1与MMP-9、NF．KBp65蛋白表达呈显著负相关关系（rs=-0．547,P〈0．05;rs=-0．414,P〈0．05）;MMP-9与NF-κBp65蛋白表达呈显著正相关关系（rs=0．695,P〈0．05）。结论 KiSS-1基因可能对卵巢癌的转移起一定的抑制作用;KiSS-1基因可能通过抑制MMP-9、NF-κB基因,从而发挥抑制卵巢癌转移的作用。     

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.     

The role of actin bundling protein fascin in the progression of ovarian neoplasms

PURPOSE OF INVESTIGATION: The aim of the study was to investigate the role of fascin in tumor progression and to investigate the role of fascin on endothelial cell migration and angiogenesis in ovarian neoplasms. METHODS: In the study, 94 malign epithelial ovarian neoplasms, 13 borderline epithelial ovarian neoplasms, 25 serous and mucinous cystadenomas and four normal ovarian tissues were examined by means of immunohistochemistry, using monoclonal antihuman fascin antibody, clone IM20. RESULTS: Total stromal fascin score in cases of borderline and malign epithelial ovarian tumors was significantly higher compared to normal ovaries and benign epithelial ovarian tumors (.000, p < 0.001). There was no statistically significant difference in terms of total epithelial fascin scores of samples between groups (.080, p > 0.05). Presence of vascular invasion (.000, p < 0.001), psammomatous calcifications (.001, p = 0.001), and lymphocytic infiltration (.000, p < 0.001) were significantly higher in malign neoplasms. There was no significant difference in terms of mean microvessel count and homogeneous or heterogeneous fascin expression of microvessels between the benign and malign groups (respectively p = .228 and p = .143). CONCLUSIONS: This study suggests that up-regulation of fascin in tumoral tissue may promote invasion of ovarian carcinoma by cell-matrix adhesion.     

肺内结节间质病变

病例1资料：患儿女,6岁。反复咳嗽、咯血,面色苍白;血红蛋白66 g/L,小细胞低色素性贫血;痰涂片检查可见含铁血黄素巨噬细胞。         影像表现：两肺透光度减低,广泛磨玻璃征,肺内弥漫分布密度较淡、轮廓模糊的小结节,小叶间隔增厚呈细网状影。     

CyclinD1、C-erbB2及bcl-2基因在卵巢上皮性肿瘤中的表达及其临床意义

目的 :检测癌基因CyclinD1、C erbB2及bcl 2在卵巢上皮肿瘤中的表达 ,探讨它们在卵巢肿瘤发生、发展中的作用及临床、病理意义。方法 :应用免疫组化SP法检测72例恶性卵巢肿瘤、12例交界性卵巢肿瘤、2 1例良性肿瘤及 10例正常卵巢组织中Cy clinD1、C erbB2及bcl 2基因的表达情况。结果 :1.卵巢恶性、交界性及良性肿瘤中Cy clinD1阳性率依次为 2 7.78%、33.3%、9.5 2 %。恶性及交界性肿瘤阳性率明显高于良性肿瘤 ,其阳性率与组织学分级呈负相关 ,而与患者年龄、临床分期、组织学类型无关 ;2 .卵巢恶性、交界性及良性肿瘤中C erbB2的阳性率依次为 5 6 .9%、4 1.6 7%、14.2 8%。恶性及交界性肿瘤阳性率明显高于良性肿瘤 ,差异有显著性。C erbB2阳性表达在组织分化差及期别晚的肿瘤中较分化好、期别早者高 ;3.卵巢恶性、交界性、良性肿瘤中bcl 2的阳性表达率依次为 6 3.89%、5 0 %、2 8.5 %。恶性及交界性肿瘤与良性肿瘤之间的表达差异有显著性。组织分化差、期别早的肿瘤中bcl 2的阳性率较分化好、期别晚者高 ;4 .两种及两种以上基因同时表达率 (5 1.4 % )显著高于单基因表达 (2 7.79% )。CyclinD1与C erbB2基因表达呈负相关。结论 :CyclinD1、C erbB2及bcl 2基因在卵巢癌发生、发展中起重要作用 ,表明细胞?     

Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors

PURPOSE OF INVESTIGATION: To determine the expression of matrix metalloproteinase-9 (MMP-9) expression in malignant and borderline ovarian tumors and its correlation to prognosis. METHODS: Forty-five patients with primary epithelial ovarian tumors were enrolled in this retrospective study from 1988 to 2002. Only malignant (n = 30) and borderline (n = 15) ovarian tumors constituted the study group. All cases were surgically staged according to FIGO criteria. Patient characteristics and clinico-pathological findings were obtained from hospital records. Paraffin-embedded tissue blocks were treated with MMP-9 immunohistochemical stain. The percentage of the total number of tumors staining positively was categorised and awarded a score of 0 to 4: < 5% as 0, < or = 6-25% as 1, 26-50% as 2, 51-75% as 3 and 76-100% as 4. The intensity of immunostaining was scored on a 3-point scale: 1, weak; 2, moderate and 3, intense. A weighed score for each tumor specimen was produced by multiplying the percentage score with the intensity score and was defined as the 'epithelial MMP-9 score'. Stromal staining was also assessed as weak, moderate and intense. Cases with final epithelial MMP-9 scores < or = 6 and > 6 were then recategorised into two groups, accordingly. Based on degree of stromal staining, cases were recategorised into two final groups as mildly stained and intense or moderately stained. Tumor stages were regrouped as early (Stage I-II) and late (Stage III-IV), respectively. RESULTS: Mean ages of cases with malignant and borderline ovarian tumors were 57.2 +/- 3.1 and 49.7 +/- 2.1 years, respectively. Epithelial MMP-9 scores were higher in malignant tumors compared to borderline tumors (p = 0.014). However, with regard to stromal MMP-9 staining, no significant difference was observed among malignant and borderline tumors (p = 0.113). Among malignant ovarian tumors, epithelial MMP-9 scores did not differ between early versus late-staged and well versus poorly differentiated tumors. Median survival time of cases with epithelial MMP-9 scores < or = 6 and > 6 were 24 months and 32 months, respectively (log-rank: 0.93, p = 0.335). Cases with weak stromal MMP-9 staining had a longer median survival (48 months) compared to cases with moderate or intense stromal MMP-9 staining (24 months, log-rank: 4.46, p = 0.03). CONCLUSION: Epithelial MMP-9 expression generally appears in the malignant form of ovarian tumors compared to borderline tumors. MMP-9 expression in the stroma but not in the epithelium contributes to poor survival in ovarian cancers.