宫颈癌血管内皮生长因子表达与血管生成癌细胞增殖及侵袭转移的关系

目的　研究血管内皮生长因子 (VEGF)在早期宫颈癌的表达和临床意义。方法　采用免疫组织化学SP法检测 1998年 1月至 2 0 0 2年 2月期间 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VEGF的表达情况 ,并检测其中微血管密度 (MVD ,CD3 4 标记 )和癌细胞增殖标记指数 (Ki 6 7标记 )。结果　从NCE→CIN→ICC ,VEGF、Ki 6 7的阳性表达率和MVD均显著升高 (P <0 0 5 )。VEGF在ICC的表达与MVD显著正相关 (r =0 6 0 2 ,P <0 0 1) ,与盆腔淋巴结转移、脉管浸润、组织学分级和Ki 6 7表达显著相关 (P <0 0 5 ) ,但与年龄、FIGO分期、组织学类型和间质浸润无关 (P >0 0 5 )。低分化、盆腔淋巴结转移、脉管浸润及Ki 6 7高度表达者 ,与VEGF阳性表达显著相关 (P <0 0 5 )。结论　VEGF阳性表达可能在宫颈癌血管生成、癌细胞增殖、癌细胞侵袭转移中起重要作用。VEGF检测对进一步了解宫颈癌生物学行为和判断其预后具有一定的临床应用价值。     

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     

基质金属蛋白酶9及其抑制剂在异位和在位子宫内膜组织中的表达

目的　探讨基质金属蛋白酶 9(MMP 9)及其抑制剂———金属蛋白酶组织抑制因子(TIMP)在子宫内膜异位症患者的异位和在位内膜组织中的表达。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 ) ,分别检测 4 5例子宫内膜异位症患者 (研究组 )的异位和子宫内膜及 32例子宫肌瘤患者 (对照组 )的子宫内膜组织中MMP 9、TIMP 1的表达。结果　研究组异位和在位内膜及对照组子宫内膜组织中 ,MMP 9的表达分别为 0 381、0 336、0 2 76 ;TIMP 1的表达分别为0 2 39、0 2 5 3、0 2 6 7;研究组异位及在位内膜、对照组子宫内膜组织中MMP 9/TIMP 1的比值分别为1 5 94 ,1 2 93,1 0 34。研究组异位及在位子宫内膜组织中MMP 9、MMP 9/TIMP 1分别与对照组比较 ,差异均有显著性 (P <0 0 1,P <0 0 5 ) ;研究组异位内膜组织中TIMP 1的表达与对照组比较 ,差异也有极显著性 (P <0 0 1) ;整个月经期 ,异位内膜组织中MMP 9表达升高 ,TIMP 1表达降低 ;在位内膜MMP 9表达升高 ,其中异位内膜比在位内膜MMP 9表达升高仅发生于增殖期。结论　异位子宫内膜组织中MMP 9、TIMP 1表达的变化可能与子宫内膜异位症的发生、发展有关。     

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     

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     

分化抑制因子-1在宫颈癌组织中表达及其与微血管密度的关系

目的探讨分化抑制因子-1(Id-1)在宫颈癌组织中的表达及其与肿瘤发生、发展以及血管生成的关系。方法 2009年2月至2010年6月在吉林大学第二临床医院采用免疫组化法检测35例宫颈浸润癌(ICC)组织及20例正常宫颈上皮组织(NCE)中Id-1和微血管密度(MVD)的表达。结果 Id-1蛋白在宫颈癌组织中阳性表达率为71.43%,正常宫颈上皮组织中阳性表达率为0,两组比较有统计学意义(P<0.01),ICC组Id-1高表达与组织分化程度、间质浸润深度和盆腔淋巴结转移相关(P﹤0.05),而与FIGO分期无关(P﹥0.05);MVD计数在宫颈癌组织中表达为46.57±10.291,在正常宫颈上皮组织中为12.40±3.761,两组比较有统计学意义(P<0.05),MVD的表达在ICC组内与盆腔淋巴结转移、组织分化程度有关(P﹤0.05),而与FIGO分期、间质浸润深度无关(P﹥0.05);ICC组中Id-1表达强度与MVD呈正相关(r=0.648,P﹤0.01)。结论 Id-1因子通过促进肿瘤血管生成,从而参与宫颈癌的发生发展;子宫颈癌组织中的MVD值随着Id-1因子表达强度的增加而增高。阻断Id-1因子在子宫颈癌中的表达,有望成为治疗宫颈癌的途径之一。     

基质金属蛋白酶2,9在胎膜早破产妇胎膜的表达变化

目的:探讨基质金属蛋白酶- 2、- 9(MMP - 2、MMP - 9)在胎膜早破(PROM)发病机制中的作用。方法:选择早产PROM(PPROM)产妇1 1例、足月PROM产妇32例及足月临产产妇1 6例作为研究组,1 1例足月未临产产妇作为对照组;采用免疫组织化学法检测胎膜宫颈部和宫体部中MMP 2及MMP - 9的分布与表达。结果:①各研究组宫颈部胎膜MMP 2的表达均高于同组宫体部(P <0 .0 5 ) ;胎膜(宫颈部和宫体部)MMP - 2的表达在两PROM组间无差异(P >0 .0 5 ) ,但均高于足月临产组和对照组(P <0 .0 1 )。②MMP - 9在对照组中未见表达;MMP - 9在研究组胎膜宫颈部的表达均明显高于宫体部(P <0 .0 1 ) ,其中PPROM组宫颈部胎膜MMP 9表达的IH积分明显高于其余各组(P <0 .0 1 )。③胎膜宫颈部MMP - 2的表达与MMP 9的表达呈正相关(P =0 .0 0 0 )。结论:MMP -2和MMP - 9参与了产程中胎膜的破裂,在PROM的发病机制中起着重要的作用,其中MMP - 9在PPROM发病机制中的作用更为重要。     

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     

基质金属蛋白酶MMP-9及其抑制剂TIMP-1在外阴癌中的表达

目的　观察基质金属蛋白酶MMP 9和其抑制剂TIMP 1在外阴癌组织中的表达情况 ,探讨其与外阴癌的浸润及转移的关系。方法　采用免疫组织化学SP方法对 33例外阴癌、2 3例VIN、15例外阴色素减退疾病、14例外阴尖锐湿疣和 12例正常皮肤组织进行标记及分析。结果　MMP 9、TIMP 1蛋白在以上 5组细胞浆中的阳性表达分别为 31/33、2 4 /33,2 1/2 3、19/2 3,15 /15、13/15 ,12 /14、12 /14 ,10 /12、7/12。MMP 9、TIMP 1蛋白在外阴癌、VIN、色素减退疾病、尖锐湿疣中的阳性表达率与正常对照组相比差异均无显著性意义 (P >0 0 5 ) ,但在(-～ +)组与 (++～ +++)组表达率之间MMP 9在外阴癌组与其他各组间相比差异均有显著性意义 (P<0 0 5 ) ;TIMP 1在外阴癌组与色素减退疾病组和正常组相比差异有显著性意义 (P <0 0 5 )。这 2个指标在外阴癌中的表达与临床病理特征无明显相关性。在外阴癌中MMP 9与TIMP 1在阳性表达之间差异有显著性意义 (P <0 0 5 ) ,而强阳性表达间差异有极显著性意义 (P <0 0 1)。结论　在外阴癌中MMP 9的表达强度超过TIMP 1时可能是外阴癌侵袭的一个早期指标 ,但不能单独作为预测外阴癌结局的一个标志。     

基质金属蛋白酶MMP-2 MMP-9及其抑制因子TIMP-1TIMP-2在子宫内膜异位症中的表达及意义

目的　研究基质金属蛋白酶MMP 2、9和组织抑制因子TIMP 1、2在子宫内膜异位症中的表达及意义。方法　 2 0 0 0年 3月至 2 0 0 2年 4月应用免疫组化S P法检测卵巢巧克力囊肿 4 5例的异位内膜和其中 2 0例在位内膜 ,以及 2 2例正常子宫内膜中MMP 2、9及TIMP 1、2的表达。结果　异位内膜组织中MMP 2、9和TIMP 1、2的表达均显著高于在位内膜和正常内膜 (P <0 0 1)。在位内膜和正常子宫内膜组织细胞中的表达率比较 ,差异无显著性 (P >0 0 5 )。子宫内膜异位症组织中MMP 2、9的表达与侵袭程度正相关。TIMP 1、2的表达则与侵袭程度呈负相关。结论　MMP 2、9是检测子宫内膜异位症较好的分子标志 ,人工诱导TIMP 1、2或阻断MMP 2、9的表达可能抑制内异症的发生发展 ,有望成为子宫内膜异位症治疗新的辅助手段     

宫颈鳞癌和腺癌中微血管密度和基质金属蛋白酶-2 、9及其抑制剂-1、2表达的研究

目的通过观察肿瘤微血管密度(MVD)及MMP-2、MMP-9和TIMP-1、TIMP-2在宫颈鳞癌与腺癌组织中的表达情况,在蛋白水平探讨宫颈腺癌较鳞癌恶性程度高的可能原因.方法采用免疫组织化学方法(SP) 检测40例宫颈鳞癌和20例宫颈腺癌组织的MVD和MMP-2、MMP-9、TIMP-1、TIMP-2蛋白的表达情况.结果MVD在宫颈腺癌中较鳞癌高.MMP-2在宫颈鳞癌的阳性表达强度较腺癌高(P=0.006);MMP-9、TIMP-1在腺癌的阳性表达较鳞癌高(P=0.078,P=0.000);TIMP-2在两组间比差异无显著性(P＞0.05).在宫颈癌的临床病理特征中,MMP-2和MMP-9在鳞癌和腺癌中的表达不一,而TIMP-1始终是在腺癌中的表达较鳞癌高.结论宫颈腺癌较鳞癌恶性程度高的原因,可能与较高的MVD和TIMP-1的高表达有关.     

Expression of matrix metalloproteinase-2 in preinvasive and invasive carcinoma of the uterine cervix

PURPOSE: To study the immunohistochemical expression of matrix metalloproteinase-2 (MMP-2) in preinvasive and invasive carcinoma of the uterine cervix so as to demonstrate whether the expression of MMP-2 is an early or late event in the process of dedifferentiation and cancer progression. METHODS: A total number of 50 samples of cervical tissue were studied for MMP-2 immunoreactivity. The cases were selected to include ten normal cases used as a control group, 20 CIN cases and 20 cervical carcinoma cases. The CIN group was subdivided into CIN1 (n = 7), CIN2 (n = 6) and CIN3 (n = 7), while the carcinoma group was represented by squamous cell carcinoma (n = 16) and adenocarcinoma (n = 4). RESULTS: MMP-2 expression was totally absent in control cervices and low-grade squamous intraepithelial lesions, while high-grade squamous intraepithelial neoplasia and invasive carcinoma showed up-regulation of MMP-2 expression with no significant difference concerning the type of carcinoma. This overexpression of MMP-2 points to the possibility that it is an early marker of tumor progression in cervical carcinoma. CONCLUSIONS: MMP-2 has a key role in extracellular matrix degradation and invasion in carcinoma of the uterine cervix. Its expression in high-grade squamous intraepithelial lesions may denote a potential risk for invasion and metastasis.     

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.     

压力性尿失禁患者阴道壁结缔组织MMP-2及其抑制物的表达

目的:探讨女性压力性尿失禁(SUI)患者阴道壁结缔组织中基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶组织抑制物-2(TIMP-2)mRNA表达与SUI发病的关系。方法:7例无SUI妇女为对照组(A组),24例有完整随访资料的女性SUI患者的阴道壁结缔组织标本为研究组,分为<60岁组(B组)和>60岁组(C组)。应用逆转录-聚合酶链反应分别检测MMP-2和TIMP-2表达量。结果:SUI组患者的MMP-2均较非SUI组显著升高,差别有显著性(P<0.01),TIMP-2均显著下降,差异有统计学意义(P<0.01)。MMP-2在B组和C组之间的差异无显著性(P>0.05),TIMP-2的mRNA表达量C组较B组显著下降,差别有统计学意义(P<0.01)。MMP-2/TIMP-2从A组到B组再到C组显著升高,A组相似文献   

Stromal cells play a role in cervical cancer progression mediated by MMP-2 protein

Metalloproteinases, especially metalloproteinase-2 (MMP-2), are known for their role in the degradation of the extracellular matrix. Nevertheless, a thorough understanding of MMP-2 expression in neoplastic lesions of the uterine cervix has yet to be accomplished. This study aimed to analyze the MMP-2 expression in cervical intraepithelial neoplasia III (CIN3) and in cervical squamous cell carcinoma, in tumor cells and adjacent stromal cells. MMP-2 expression was assessed by an immunohistochemical technique. MMP-2 expression was greater in the stromal cells of invasive carcinomas than in CIN3 (p < 0.0001). MMP-2 expression in stromal cells correlates with the clinical stage, gradually increasing as the tumor progresses (p = 0.04). This study corroborates that stromal cells play an important role in tumor invasion and progression, mediated by the progressive enhancement of MMP-2 expression from CIN3 to advanced invasive tumor. The intense MMP-2 expression most probably is associated with poor tumor prognosis.     

MMP-1 and MMP-2 in the cervix uteri in different steps of malignant transformation--an immunohistochemical study.

OBJECTIVES: Enzymatic degradation of the extracellular matrix (ECM) represents a key element in the multistage process of tumor invasion and metastasis. This process requires extensive degradation of ECM components such as basement membrane collagen (type IV) and interstitial collagen (type I, II, III). Matrix metalloproteinase-2 (MMP-2) specifically cleaves collagen type IV, the major collagen of the basement membrane. MMP-1 digests interstitial collagen type I and III, the main collagen types of the stromal extracellular matrix. We investigated protein levels of MMP-1 and MMP-2 in different stages of malignant transformation. METHODS: Using the APAAP method we analyzed 10 normal cervical tissues, 11 cervical intraepithelial neoplasia 1 (CIN 1), 8 CIN 2 and 10 CIN 3 lesions, and 15 invasive squamous cell carcinomas. These data were compared with the HPV DNA status tested by hybrid capture II. RESULTS: Only a few isolated epithelial cells stained positively for MMP-1 and MMP-2 in normal cervical tissue and CIN 1 lesions. The CIN 2 and CIN 3 group displayed a heterogeneous distribution of MMP expression. 3 CIN 2 and 8 CIN 3 lesions showed strong MMP-2 and weak MMP-1 expression in the dysplastic epithelial cells. 5 CIN 2 and 2 CIN 3 lesions stained negatively. Invasive carcinomas showed a coexpression for MMP-1 and MMP-2 in malignant epithelial cells and peritumoral stroma cells. All MMP-2-positive cases tested positive for the HPV high-risk group. CONCLUSIONS: The expression of MMP-2 protein in preinvasive lesions of the cervix uteri and a consecutive coexpression of MMP-1 and MMP-2 in invasive cancer suggest a gradually increasing invasive potential. MMP-2 expression, when focally observed in high-grade squamous intraepithelial lesions of the cervix, may indicate tumor areas with an increased risk for invasive growth.     

MMP-2 and TIMP-2 expression correlates with poor prognosis in cervical carcinoma--a clinicopathologic study using immunohistochemistry and mRNA in situ hybridization.

OBJECTIVE: The spread of malignant neoplasms is closely associated with matrix and basement membrane degradation, mediated by various classes of proteolytic enzymes. Matrix metalloproteinases (MMP) appear to have a key role in the sequence of events that lead to local invasion and metastasis. The present study evaluated the role of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinases-2 (TIMP-2), and membrane-type metalloproteinase (MT1-MMP) in cervical neoplasia. METHODS: We have analyzed 49 uterine cervical squamous cell carcinomas, 10 cases of high-grade cervical intraepithelial neoplasia (CIN II-III), and 10 control cervices for the presence of MMP-2, TIMP-2, and MT1-MMP using in situ hybridization. MMP-2 protein expression was evaluated using immunohistochemistry. Results were analyzed for possible correlation with disease outcome. RESULTS: MMP-2, TIMP-2, and MT1-MMP mRNA were localized to both stromal and tumor cells. However, an intense signal for MMP-2 was detected almost exclusively in tumor cells and was uniformly absent from CIN lesions and control cervices. Conversely, intense signals for TIMP-2 and MT1-MMP were detected in both stromal and tumor cells of invasive carcinomas, more often for the former. As with MMP-2, they were absent from CIN lesions. MMP-2 protein expression was enhanced in tumor cells compared to CIN cases and controls, significantly compared to the latter (P = 0.01). The presence of both MMP-2 and TIMP-2 mRNA in tumor cells correlated with advanced stage (P = 0.003 for MMP-2, P = 0.002 for TIMP-2) and with poor survival (P = 0.003 for MMP-2, P = 0.002 for TIMP-2) in univariate analysis. In addition, their presence in tumor cells intercorrelated (P = 0.002). In multivariate survival analysis, MMP-2 presence retained its association with survival (P = 0.004), in addition to patient age (P = 0.027) and advanced stage (P = 0. 0002). CONCLUSIONS: Both MMP-2 and TIMP-2 have a key role in extracellular matrix invasion in cervical carcinoma, largely through their elaboration by tumor cells. The presence of mRNA for both proteins is interrelated and is associated with poor survival.     

阴道壁结缔组织中基质金属蛋白酶及其组织抑制物的表达

目的探讨女性压力性尿失禁(SUI)患者阴道壁结缔组织中基质金属蛋白酶(MMP)9及其组织抑制物(TIMP)1的mRNA表达变化及其与SUI发病的关系。方法收集24例有完整随访资料的女性SUI患者的阴道壁结缔组织标本作为研究组,根据年龄不同分为>60岁和≤60岁两类,每组12例;另选7例非SUI妇女作为对照组,应用RT-PCR法检测MMP-9和TIMP-1mRNA表达量。以MMP-9、TIMP-1与内参照3-磷酸甘油醛脱氢酶(GAPDH)基因的扫描灰度,计算曲线下峰面积作为PCR产物含量。结果(1)研究组中>60岁和≤60岁者MMP-9mRNA的表达量分别为0·56±0·20和0·56±0·19,均高于对照组的0·37±0·18,分别比较,差异均有统计学意义(P<0·05);>60岁和≤60岁者MMP-9mRNA的表达量比较,差异无统计学意义(P>0·05)。(2)研究组中>60岁和≤60岁者TIMP-1mRNA的表达量分别为0·23±0·11和0·31±0·12,均低于对照组的0·41±0·13,分别比较,差异均有统计学意义(P<0·05),TIMP-1mRNA的表达量在>60岁和≤60岁者间比较,差异也有统计学意义(P<0·05)。(3)MMP-9/TIMP-1比值,研究组中>60岁和≤60岁者及对照组分别为2·49±1·82、1·82±1·58、0·90±1·38,分别比较,差异均有统计学意义(P<0·05)。结论SUI患者MMP-9的高表达和TIMP-1的低表达,导致MMP/TIMP比值升高,年龄越大,MMP/TIMP比值升高越显著;MMP与TIMP比例失衡,在SUI的发病过程中可能起重要作用。     

MMP-9及TIMP-1在子宫腺肌病中的表达及临床意义

目的:研究MMP-9和TIMP-1在子宫腺肌病中的表达,探讨其在子宫腺肌病发病机制中的作用。方法:采用免疫组化方法检测子宫腺肌病中MMP-9、TIMP-1的表达。结果:MMP-9、TIMP-1在子宫腺肌病异位内膜中表达的阳性率均高于在位内膜及正常子宫内膜(P<0.05),二者在在位内膜与正常子宫内膜的表达差异无统计学意义(P>0.05);子宫腺肌病患者痛经的程度随MMP-9、TIMP-1在异位子宫内膜中表达程度的增高而增高(P<0.05)。结论:MMP-9和TIMP-1的异常表达与子宫腺肌病的发生和生物学行为有关。异位内膜中MMP-9和TIMP-1过度表达与子宫腺肌病痛经的发生有关。