李青,陈陆俊,谢军,鲁常青,田波,虞华明,樊祥山

• 1:常州市第一人民医院病理科
• 2:常州市第一人民医院综合实验室
• 3:南京市鼓楼医院病理科

摘要(Abstract)：

目的探讨MT2-MMP在子宫颈癌变过程中表达水平的变化及其与瘤内血管生成的关系。方法采用组织芯片技术和免疫组织化学方法,分别检测子宫颈上皮内瘤变(CIN)和子宫颈鳞状细胞癌组织中膜型基质金属蛋白酶MT2-MMP的表达和瘤内微血管分布。结果 MT2-MMP在正常子宫颈组织中以不表达或低表达为主,而在子宫颈癌变过程中其表达水平显著上调。子宫颈鳞癌Ⅲ级及CINⅡ～Ⅲ级的患者,其MT2-MMP的表达水平显著高于CINⅠ级的患者(子宫颈鳞癌Ⅲ级vs CINⅠ级,P=0.0009;CINⅡ～Ⅲ级vs CINⅠ级,P=0.0323),子宫颈鳞癌Ⅰ～Ⅱ级的患者,其MT2-MMP的表达水平亦高于CINⅠ级的患者(P=0.0807);同时,子宫颈癌变过程中,MT2-MMP的表达水平和瘤内微血管密度呈显著正相关(r=0.3176,P=0.0015)。结论 MT2-MMP参与子宫颈鳞癌的发生与发展,并参与促进瘤内微血管的形成,其作为子宫颈鳞癌诊断和治疗潜在分子靶标的临床应用价值,值得进一步研究。

关键词(KeyWords)： 宫颈肿瘤;微血管密度;组织芯片;基质金属蛋白酶;免疫组织化学

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 李青,陈陆俊,谢军,鲁常青,田波,虞华明,樊祥山

DOI: 10.13267/j.cnki.syzlzz.2011.05.013

参考文献(References)：

• [1]Kerkela E,Ala-Aho R,Jeskanen L,et al.Expression ofhuman macrophage metalloelastase(MMP-12)by tumorcells in skin cancer[J].J Invest Dermatol,2000,114(6):1113-1119.
• [2]李佩瑞,王济明.基质金属蛋白酶与肿瘤血管生成[J].中华实用医学杂志2,0046,(2):42-44.
• [3]Morrison CJ,Butler GS,Bigg HF,et al.Cellularactivation of MMP-2(gelatinase A)by MT2-MMP occursvia a TIMP-2-independent pathway[J].J Biol Chem,2001,276(50):47402-47410.
• [4]Detre S,Saclani Jotti G,Dowsett M.A“quickscore”method for immunohistochemical semiquantitation:validation for oestrogen receptor in breast carcinomas[J].J Clin Pathol,1995,48(9):876-878.
• [5]Hammes LS,Tekmal RR,Naud P,et al.Up-regulationof VEGF,c-fms and COX-2 expression correlates withseverity of cervical cancer precursor(CIN)lesions andinvasive disease[J].Gynecol Oncol,2008,110(3):445-451.
• [6]Stetler-Stevenson WG,Aznavoorian S,Liotta LA.Tumorcell interactions with the extracellular matrix duringinvasion and metastasis[J].Annu Rev Cell Biol,1993,9:541-573.
• [7]Visse R,Nagase H.Matrix metalloproteinases and tissueinhibitors of metalloproteinases:structure,function,andbiochemistry[J].Circ Res,2003,92(8):827-839.
• [8]Ueno H,Nakamura H,Inoue M,et al.Expression andtissue localization of membrane-types 1,2,and 3 matrixmetalloproteinases in human invasive breast carcinomas[J].Cancer Res,1997,57(10):2055-2060.
• [9]Davidson B,Goldberg I,Berner A,et al.Expression ofmembrane-type 1,2,and 3 matrix metalloproteinasesmessenger RNA in ovarian carcinoma cells in serouseffusions[J].Am J Clin Pathol,2001,115(4):517-524.
• [10]Asano T,Tada M,Cheng S,et al.Prognostic values ofmatrix metalloproteinase family expression in humancolorectal carcinoma[J].J Surg Res,2008,146(1):32-42.
• [11]Gilles C,Polette M,Piette J,et al.High level of MT-MMP expression is associated with invasiveness ofcervical cancer cells[J].Int J Cancer,1996,65(2):209-213.
• [12]Abraham R,Schafer J,Rothe M,et al.Identification ofMMP-15 as an anti-apoptotic factor in cancer cells[J].J Biol Chem,2005,280(40):34123-34132.
• [13]李青,陈陆俊,谈炎,等.组织因子在子宫颈病变过程中的表达及其与瘤内血管生成的关系[J].实用肿瘤杂志,20092,4(4):349-352.
• [14]Sounni NE,Devy L,Hajitou A,et al.MT1-MMPexpression promotes tumor growth and angiogenesisthrough an up-regulation of vascular endothelial growthfactor expression[J].Faseb J,2002,16(6):555-564.
• [15]张诗武,张永亮,魏焕萍,等.组织芯片技术及其应用[J].武警医学院学报2,0011,1(2):125-127.