血小板反应素-1在卵巢上皮癌组织的表达及与p53肿瘤抑制蛋白和肿瘤血管形成的关系Expression of thrombospondin-1 in epithelial ovarian cancer and its correlation with p53 tumor inhibitor protein expression and tumor angiogenesis
谭先杰;郎景和;王芊晨;沈铿;楼伟珍;许秀英;
摘要(Abstract)：
目的:检测血小板反应素-1(TSP-1)和p53肿瘤抑制蛋白在卵巢上皮癌的表达,并探讨其表达与肿瘤血管形成及患者预后的关系。方法:用免疫组化法检测57例原发性卵巢上皮癌组织和22例正常卵巢组织中TSP-1和p53蛋白的表达,并用CD34抗体免疫染色后对微血管密度(MVD)计数。结合随诊资料,回顾分析上述指标与卵巢上皮癌临床病理特征及3年存活率之间的关系。结果:卵巢上皮癌组织中TSP-1的阳性表达率低于正常卵巢组织(分别为47.4%和72.7%,P=0.042),且多为弱阳性表达;卵巢上皮癌组织中p53的阳性率为61.4%,正常卵巢组织未检测到p53蛋白。TSP-1表达和p53蛋白阳性与卵巢上皮癌的手术病理分期、大网膜转移和癌性腹水相关。卵巢上皮癌组织的MVD高于正常卵巢组织(分别30.3±8.5和20.1±8.1,P=0.014)。TSP-1表达与MVD呈负相关(P<0.001),p53蛋白阳性与MVD呈正相关(P<0.001)。TSP-1表达与患者的3年存活率呈正相关(P=0.001),p53蛋白阳性与3年存活率呈负相关(P=0.002)。TSP-1阴性而p53蛋白阳性组患者的3年存活率明显低于TSP-1阳性而p53蛋白阴性组(分别为13.6%和78.6%,P<0.001)。结论:卵巢上皮癌组织TSP-1和p53蛋白的表达与肿瘤血管形成有关,对上述分子的检测有助于临床判断卵巢上皮癌的生物学行为。
关键词(KeyWords)： 卵巢肿瘤;血小板反应素-1;蛋白质p53;肿瘤抑制蛋白质;微血管密度;血管形成;预后
基金项目(Foundation): 国家自然科学基金资助项目(No:30100199);; 北京科技新星计划资助项目(No:2003A25)
作者(Author): 谭先杰;郎景和;王芊晨;沈铿;楼伟珍;许秀英;
Email:
DOI: 10.13283/j.cnki.xdfckjz.2008.01.030
参考文献(References)：
- [1]Weidner N,Semple JP,Welch WR,et al.Tumor angiogen-esis and metastasis:correlation in invasive breast carcino-ma[J].N Engl J Med,1991,324:1-8
- [2]Lawler J.Thrombospondin-1as an endogenous inhibitor ofangiogenesis and tumor growth[J].J Cell Mol Med,2002,6:1-12
- [3]Goodheart MJ,Vasef MA,Sood AK,et al.Ovarian cancer p53mutation is associated with tumor microvessel density[J].Gynecol Oncol,2002,86:85-90
- [4]Dameron KM,Volpert OV,Tainsky MA,et al.Control of angiogenesis in fibrobalsts by p53regulation of throm-bospondin-1[J].Science,1994,265:1582-1584
- [5]Iddings DM,Koda EA,Grewal SS,et al.Association of an-giogenesis markers with lymph node metastasis in early colorectal cancer[J].Arch Surg,2007,142:738-744
- [6]Byrne GJ,Hayden KE,McDowell G,et al.Angiogenic characteristics of circulating and tumoural throm-bospondin-1in breast cancer[J].Int J Oncol,2007,31:1127-1132
- [7]Hawighorst T,Oura H,Streit M,et al.Thrombospondin-1selectively inhibits early-stage carcinogenesis and angio-genesis but not tumor lymphangiogenesis and lymphatic metastasis in transgenic mice[J].Oncogene,2002,21:7945-7956
- [8]de Fraipont F,Nicholson AC,Feige JJ,et al.Throm-bospondins and tumor angiogenesis[J].Trends Mol Med,2001,7:401-407
- [9]Sood AK,Sorosky JI,Dolan M,et al.Distant metastasis in ovarian cancer:association with p53mutations[J].Clin Cancer Res,1999,5:2485-2490
- [10]Strohmeyer D,Rossing C,Bauerfeind A,et al.Vascular endothelial growth factor and its correlation with angio-genesis and p53expression in prostate cancer[J].Pros-tate,2000,45:216-224
- [11]Karavasilis V,Malamou-Mitsi V,Briasoulis E,et al.Clin-icopathologic study of vascular endothelial growth factor,thrombospondin-1,and microvessel density assessed by CD34in patients with stage III ovarian carcinoma[J].Int J Gynecol Cancer,2006,16:241-246
- [12]Rusk A,McKeegan E,Haviv F,et al.Preclinical evalua-tion of antiangiogenic thrombospondin-1peptide mimet-ics,ABT-526and ABT-510,in companion dogs with nat-urally occurring cancers[J].Clin Cancer Res,2006,12:7444-7455
- [13]Yang Q,Tian Y,Liu S,et al.Thrombospondin-1peptide ABT-510combined with valproic acid is an effective an-tiangiogenesis strategy in neuroblastoma[J].Cancer Res,2007,67:1716-1724
- [14]Gietema JA,Hoekstra R,de Vos FY,et al.A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510with gemcitabine and cisplatin in patients with solid tumors[J].Ann Oncol,2006,17:1320-1327