TY - JOUR
T1 - Tumor microvessel density as a prognostic marker in high-risk renal cell carcinoma patients treated on ECOG-ACRIN E2805
AU - Jilaveanu, Lucia B.
AU - Puligandla, Maneka
AU - Weiss, Sarah A.
AU - Wang, Xin Victoria
AU - Zito, Christopher
AU - Flaherty, Keith T.
AU - Boeke, Marta
AU - Neumeister, Veronique
AU - Camp, Robert L.
AU - Adeniran, Adebowale
AU - Pins, Michael
AU - Manola, Judith
AU - DiPaola, Robert S.
AU - Haas, Naomi B.
AU - Kluger, Harriet M.
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-17-1555
DO - 10.1158/1078-0432.CCR-17-1555
M3 - Article
C2 - 29066509
AN - SCOPUS:85040051372
SN - 1078-0432
VL - 24
SP - 217
EP - 223
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -