Tumor microvessel density as a prognostic marker in high-risk renal cell carcinoma patients treated on ECOG-ACRIN E2805

Lucia B. Jilaveanu, Maneka Puligandla, Sarah A. Weiss, Xin Victoria Wang, Christopher Zito, Keith T. Flaherty, Marta Boeke, Veronique Neumeister, Robert L. Camp, Adebowale Adeniran, Michael Pins, Judith Manola, Robert S. DiPaola, Naomi B. Haas, Harriet M. Kluger

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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 diseasefree 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.

Original languageEnglish
Pages (from-to)217-223
Number of pages7
JournalClinical Cancer Research
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2018

Bibliographical note

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.

Publisher Copyright:
© 2018 American Association for Cancer Research.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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