骶骨脊索瘤中Survivin、VEGF的表达及其与血管生成的相关性研究Study on the correlation between the expression and the angiogenesis of survivin and VEGF in sacral chordoma
陈超;杨惠林;陈康武;陆俭;王根林;
摘要(Abstract):
[目的]研究骶骨脊索瘤组织中生存素(survivin)、血管内皮生长因子(vascular endothelial growth factor,VEGF)与微血管密度(microvessel density,MVD)的表达情况及三者的相关性,为骶骨脊索瘤的预后判断和靶向治疗提供理论依据。[方法]应用免疫组织化学(SP)法检测30例人骶骨脊索瘤组织和10例癌旁组织中survivin、VEGF的表达,利用CD34标记组织中的新生血管。[结果]①Survivin、VEGF在骶骨脊索瘤中的阳性表达率分别为70.0%、76.7%,均高于瘤旁组织(P<0.05)。骶骨脊索瘤中MVD值(27.2±10.70)/mm2高于瘤旁组织(8.90±3.11)/mm2(P<0.05);②Survivin阳性表达的骶骨脊索瘤组织中MVD值(30.71±10.35)/mm2明显高于Sur-vivin阴性组(19.00±6.25)/mm2(P<0.05)。VEGF阳性组MVD值(29.43±10.87)/mm2明显高于VEGF阴性组(19.86±6.18)/mm2(P<0.05);③Survivin与VEGF的表达呈正相关(r=0.499,P=0.005);④Survivin的表达与患者肿瘤有无局部浸润、是否复发相关(P<0.05)。[结论]骶骨脊索瘤组织中survivin和VEGF表达水平较高,两者的表达呈正相关且与骶骨脊索瘤中的MVD均呈正相关,二者对骶骨脊索瘤的血管生成可能起协同、正向调节作用。
关键词(KeyWords): 骶骨;脊索瘤;生存素;血管内皮生长因子;微血管密度;免疫组织化学
基金项目(Foundation):
作者(Author): 陈超;杨惠林;陈康武;陆俭;王根林;
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参考文献(References):
- [1]Wippold FJ 2nd,Koeller KK,Smirniotopoulos JG.Clinical and im-aging features of cervical chordoma[J].AJR,1999,5:1423-1426.
- [2]Bohlman HH,Sachs BL,Carter JR,et al.Primary neoplasms of thecervical spine.Diagnosis and treatment of twenty-three patients[J].J Bone Joint Surg Am,1986,68:483-494.
- [3]Ferrara N,Gerber HP,LeCouter J.The biology of VEGF and itsreceptors[J].Nat Med,2003,9:669-676.
- [4]Fonsatti E,Sigalotti L,Arslan P,et al.Emerging role of endoglin(CD105)as a marker of angiogenesis with clinical potential in hu-man malignancies[J].Curr Cancer Targets,2003,6:427-432.
- [5]陆珍凤,黄文斌,石群立,等.结直肠癌组织中CD105的表达及临床意义[J].诊断病理学杂志,2008,4:139-140.
- [6]Lu CD,Altieri DC,Tanigawa N.Expression of a novel anti-apop-tosis gene,Surviv in,correlated with tumor cell apoptosis and P53accumulation in gastric carcinomas[J].Cancer Res,1998,9:1808-1812.
- [7]Mattern J,Koomgi R,Volm M.Association of vascular endothelialgrowth factor expression with intratumoral microvessel density andtumor cell proliferation in human epidermoid lung cancer[J].Br JCancer,1996,73:931-934.
- [8]陈康武,杨惠林,王根林,等.骶骨脊索瘤术后复发的相关因素分析[J].中国矫形外科杂志,2009,21:1613-1616.
- [9]Fuchs B,Dickey ID,Yaszemski MJ,et al Operative managementof sacral chordoma[J].J Bone Joint Surg Am,2005,87:2211-2216.
- [10]Hulen CA,Temple HT,Fox WP,et al.Oncologic and functionalout come following sacrectomy for sacral chordoma[J].J Bone andJoint Surg Am,2006,7:1532-1539.
- [11]Yang H,Zhu L,Ebraheim NA,et al.Analysis of risk factors for re-currence after the resection of sacral chordoma combined with embo-lization[J].Spine,2009,12:972-980.
- [12]Folkmen J.Tumor angiogenesis:therapeutic implication[J].N En-gl J Med,1971,21:1182-1186.
- [13]Sund M,Hamano Y,Sugmioto H,et al.Function of endogenous in-hibitors of angiogenesis as endothelium specific tumor suppressors[J].Proc Natl Acad Sci USA,2005,102:2934-2939.
- [14]Olie RA,Simes-Wüst AP,Baumann B,et al.A novel antisenseoligonucleotide targeting survivin expression induces apoptosis andsensitizes lung cancer cells to chemotherapy[J].Cancer Res,2000,11:2805-2809.
- [15]Chiou SK,Jones MK,Tarnawski AS.Survivin-an anti-apoptosisprotein:its biological roles and implications for cancer and beyond[J].Med Sci Monit,2003,4:43-47.
- [16]LaCasse EC,Baird S,Korneluk RG,et al.The inhibitors of apopto-sis(IAPs)and their emerging role in cancer[J].Oncogene,1998,25:3247-3259.
- [17]Shin S,Sung BJ,Cho YS,et al.An anti-apoptotic protein humansurviving is a direct inhibitor of caspase-3 and-7[J].Biochem-istry,2001,40:1117-1123.
- [18]Yamamoto T,Tanidawa N.The role of survivin as a new target of di-agnosis and treamtent in human cancer[J].Med Electron Microsc,2001,4:207-212.
- [19]Xiang Y,Yao H,Wang S,et al.Prognostic value of survivin andlivin in nasopharyngeal carcinoma[J].Laryngoscope,2006,1:126-130.
- [20]Deniz ML,Kilic T,Almaata I,et al.Expression of growth factorsand structural proteins in chordomas:basic fibroblast growth factor,transforming growth factor,and fibronectin are correlated with re-currence[J].Neurosurgery,2002,3:753-760.
- [21]Tran J,Master Z,Yu JL,et al.A role for survivin in chemoresis-tance of endothelial cells mediated by VEGF[J].Proc Natl AcadSci USA,2002,99:4349-4354.
- [22]Mesri M,Morales-Ruiz M,Ackermann EJ,et al.Suppression ofvascular endothelial growth factor-mediated endothelial cell pro-tection by survivin targeting[J].Am J Pathol,2001,158:1757-1765.