Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma.
Ann Oncol
; 24(9): 2409-14, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23788753
ABSTRACT
BACKGROUND:
Previous studies suggest that expression of hypoxia markers may be associated with response to antiangiogenic drugs. Thus, we aimed to identify predictors of sunitinib outcome in clear-cell renal cell carcinoma (ccRCC). PATIENTS ANDMETHODS:
The expression of eight key proteins related to hypoxia (CAIX, HIF1A, HIF2A, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) and P-glycoprotein were assessed by immunohistochemistry in 67 primary ccRCC samples from prospectively recruited patients treated with first-line sunitinib. The proteins expression, VHL inactivation and EGLN3 mRNA content were compared with the patients' response to sunitinib.RESULTS:
High expression of HIF2A and PDGFRB was associated with better sunitinib RECIST objective response (P = 0.024 and P = 0.026; respectively) and increased VEGFR3 expression was associated with longer progression-free survival (P = 0.012). VEGFR3 overexpression showed a negative correlation with VEGFR3 polymorphism rs307826 (P = 0.002), a sunitinib resistance predictor. With respect to overall survival (OS), high VEGFA was associated with short (P = 0.009) and HIF2A with long (P = 0.048) survival times. High EGLN3 mRNA content was associated with shorter OS (P = 0.023).CONCLUSIONS:
We found an association between several proteins involved in hypoxia and sunitinib efficacy. In addition, low VEGFR3 expression was associated with worse outcome and with VEGFR3 rs307826 variant allele, reinforcing VEGFR3 as a marker of sunitinib resistance.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Carcinoma de Células Renais
/
Receptor 3 de Fatores de Crescimento do Endotélio Vascular
/
Prolina Dioxigenases do Fator Induzível por Hipóxia
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Indóis
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Neoplasias Renais
Tipo de estudo:
Observational_studies
/
Prognostic_studies
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Risk_factors_studies
Limite:
Aged80
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article