Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study
Independent prognostic relevance of microvessel density in advanced epithelial ovarian cancer and associations between CD31, CD105, p53 status, and angiogenic marker expression: A Gynecologic Oncology Group study
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DOI：
10.1016/j.ygyno.2008.11.030
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发表时间：
2009-03-01
影响因子：
4.7
通讯作者：
Secord, Angeles Alvarez
中科院分区：
文献类型：
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作者：
Rubatt, Jennifer M.;Darcy, Kathleen M.;Secord, Angeles Alvarez
目标.本研究的目的是探讨微血管密度（MVD）在既往未经治疗的晚期上皮性卵巢癌（EOC）中的预后意义，并探讨MVD与影响血管生成的因素之间的关系。通过免疫组化CD 31或CD 105在106例接受GOG随机III期试验治疗的妇女肿瘤切片中的表达来确定MVD。平均MVD热点通过光学显微镜在高功率（x400）下定量，并分类为低（<上四分位数）或高（>=上四分位数）。MASPIN、THBS-1、bFGF、VEGF、VEGFR-1和p53状态（突变和过表达）的免疫印迹表达预先确定。在106例可评估的病例中，25%的病例显示高CD 31-MVD（>24.25支血管/高倍视野[HPF]）或高CD 105-MVD（>19.25支血管/HPF）。校正年龄并按GOG体能状态、分期、细胞类型、分级、减积状态和治疗方案分层后，高vs低CD 105-MVD与疾病进展风险增加相关（风险比[HR] = 1.873; 95%置信区间[CI]：1.102-3.184; p = 0.020）。但不是死亡（HR = 1.125; 95% CI：0.654-1.935; p = 0.670）而CD 31-MVD与疾病进展风险无关（HR = 1.578; 95% CI=0.918-2.711; p = 0.099）或死亡（HR = 1.678：95% CI = 0.957-2.943; p=0.071）。CD 31-MVD与CD 105-MVD（p=0.001）和MASPIN（p=0.016）相关。CD 31-MVD和CD 105-MVD与p53状态、THBS-1、bFGF、VEGF和VEGFR-1均无相关性。使用CD 105（增殖内皮细胞和新血管生成的标志物）而非CD 31（泛内皮标志物）评估的高MVD似乎是晚期EOC女性患者在校正预后临床协变量后无进展生存期较差的独立预后因素。(C)2008年爱思唯尔公司All rights reserved.
Objectives. The aims of this study were to examine Prognostic significance of microvessel density (MVD) in previously-untreated, advanced epithelial ovarian cancer (EOC) and explore associations between MVD and factors that affect angiogenesis.Methods. MVD was determined by immunohistochemical expression of CD31 or CD105 in tumor sections from 106 women treated on GOG randomized phase III trials. Average MVD hotspots were quantified by light microscopy at high power (x400) and categorized as low (< upper quartile) or high (>= upper quartile). Immunoblot expression of MASPIN, THBS-1, bFGF, VEGF, VEGFR-1 and p53 status (mutation and overexpression) was previously determined.Results. Of 106 evaluable cases, 25% exhibited high CD31-MVD (>24.25 vessels/high power field [HPF]) or high CD105-MVD (>19.25 vessels/HPF). After adjusting for age and stratifying by GOG performance status, stage, cell type, grade, debulking Status and treatment regimen, high Versus low CD105-MVD was associated with increased risk of disease progression (hazard ratio [HR] = 1.873; 95% confidence interval [CI]: 1.102-3.184; p = 0.020). but not death (HR = 1.125; 95% CI: 0.654-1.935; p = 0.670) whereas CD31-MVD was not associated with risk of disease progression (HR = 1.578; 95% CI=0.918-2.711; p = 0.099) or death (HR = 1.678: 95% CI = 0.957-2.943; p=0.071). CD31-MVD was correlated with CD105-MVD (p=0.001) and MASPIN (p=0.016). Neither CD31-MVD nor CD105-MVD was associated with p53 status, THBS-1, bFGF, VEGF or VEGFR-1.Conclusions. High MVD assessed using CD105, a marker of proliferating endothelial cells and neoangiogenesis, but not CD31 a pan-endothelial marker, appeared to be an independent prognostic factor for worse progression-free survival in women with advanced EOC after adjusting for prognostic clinical covariates. (C) 2008 Elsevier Inc. All rights reserved.