Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805.
Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805.
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DOI：
10.1158/1078-0432.ccr-17-1555
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Kluger HM
中科院分区：
文献类型：
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作者：
Jilaveanu LB;Puligandla M;Weiss SA;Wang XV;Zito C;Flaherty KT;Boeke M;Neumeister V;Camp RL;Adeniran A;Pins M;Manola J;DiPaola RS;Haas NB;Kluger HM
肾细胞癌（RCC）是一种常见的恶性肿瘤。微血管密度（MVD）是肿瘤血管生成的一种测量方法，但其作为预后生物标志物的效用尚不清楚。ECOG-ACRIN 2805（E2805）入组了1，943例切除的高危RCC患者，随机接受舒尼替尼、索拉非尼或安慰剂辅助治疗。我们的目的是确定微血管密度在肾细胞癌的预后和预测作用。我们在E2805上从822例患者中获得治疗前的原发性RCC肾切除组织，并构建组织芯片。使用定量免疫荧光法，我们测量肿瘤MVD作为CD 34表达细胞的面积。我们确定了与无病生存期（DFS），总生存期（OS），治疗组和临床病理变量的关系。对于整个队列（p=0.021）和接受安慰剂治疗的患者（p =0.028），高MVD（高于中位数）与OS延长相关。在接受舒尼替尼或索拉非尼治疗的患者中，高MVD与OS之间的相关性较弱（p=0.060）。MVD与DFS无关（p=1.00）。在多变量分析中，MVD仍然与OS改善独立相关（p=0.013）。高MVD与Fuhrman分级1-2（p<0.001）、透明细胞组织学（p<0.001）和无坏死（p<0.001）相关，但与性别、年龄、肉瘤样特征、淋巴管浸润或肿瘤大小无关。高MVD在切除的高危肾细胞癌患者是一个独立的预后，而不是预测，改善OS的生物标志物。进一步的研究应评估是否将MVD纳入临床模型将提高我们的能力来预测结果，如果低MVD可用于选择高危患者的辅助治疗试验。
Increased vascularity is a hallmark of renal cell carcinoma (RCC). Microvessel density (MVD) is one measurement of tumor angiogenesis, however its utility as a biomarker of outcome is unknown. ECOG-ACRIN 2805 (E2805) enrolled 1,943 resected high-risk RCC patients randomized to adjuvant sunitinib, sorafenib, or placebo. We aimed to determine the prognostic and predictive role of MVD in RCC. We obtained pre-treatment primary RCC nephrectomy tissues from 822 patients on E2805 and constructed tissue microarrays. Using quantitative immunofluorescence we measured tumor MVD as the area of CD34-expressing cells. We determined the association with disease-free survival (DFS), overall survival (OS), treatment arm and clinicopathologic variables. High MVD (above the median) was associated with prolonged OS for the entire cohort (p=0.021) and for patients treated with placebo (p=0.028). The association between high MVD and OS was weaker in patients treated with sunitinib or sorafenib (p=0.060). MVD was not associated with DFS (p=1.00). On multivariable analysis, MVD remained independently associated with improved OS (p=0.013). High MVD correlated with Fuhrman grade 1-2 (p<0.001), clear cell histology (p<0.001), and absence of necrosis (p<0.001) but not with gender, age, sarcomatoid features, lymphovascular invasion, or tumor size. High MVD in resected high-risk RCC patients is an independent prognostic, rather than predictive, biomarker of improved OS. Further studies should assess whether incorporating MVD into clinical models will enhance our ability to predict outcome and if low MVD can be used for selection of high risk patients for adjuvant therapy trials.
影响因子：
3.7
作者：
Jilaveanu LB;Zhao F;Zito CR;Kirkwood JM;Nathanson KL;D'Andrea K;Wilson M;Rimm DL;Flaherty KT;Lee SJ;Kluger HM
通讯作者：
Kluger HM