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.

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Published in Clinical Cancer Research, v. 24, issue 1, p. 217-223.

© 2017 American Association for Cancer Research

The copyright holder has granted the permission for posting the article here.

The document available for download is the authors' post-peer-review final draft of the article.

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Funding Information

This work was supported by CA180820, CA180794, CA180826, and in part by NIH grants R-01 CA158167 and K24 CA172123 (to H.M. Kluger, principal investigator). L.B. Jilaveanu is also supported by the Lung Cancer Research Foundation-LUNGevity and Melanoma Research Alliance Award #308721.

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Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

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Supplementary Data