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Clin Cancer Res. 2018 Jan 1;24(1):217-223. doi: 10.1158/1078-0432.CCR-17-1555. Epub 2017 Oct 24.

Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell Carcinoma Patients Treated on ECOG-ACRIN E2805.

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Division of Medical Oncology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Biology, University of Saint Joseph, School of Health and Natural Sciences, West Hartford, Connecticut.
Division of Hematology/Oncology, Department of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.
Department of Urology, Yale University School of Medicine, New Haven, Connecticut.
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Department of Pathology, Advocate Lutheran General Hospital, Park Ridge, Illinois.
University of Kentucky School of Medicine, Lexington, Kentucky.
Department of Medicine, Division of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Division of Medical Oncology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
Contributed equally


Purpose: 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.Experimental Design: We obtained pretreatment 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.Results: 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.Conclusions: 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. Clin Cancer Res; 24(1); 217-23. ©2017 AACR.

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