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Prospective study assessing hypoxia-related proteins as markers for the outcome of treatment with sunitinib in advanced clear-cell renal cell carcinoma.

Authors: Garcia-Donas, J  Leandro-García, L J  González Del Alba, A  Morente, M  Alemany, I  Esteban, E  Arranz, J A  Climent, M A  Gallardo, E  Castellano, D E  Bellmunt, J  Mellado, B  Puente, J  Moreno, F  Font, A  Hernando, S  Robledo, M  Rodríguez-Antona, C 
Citation: Garcia-Donas J, etal., Ann Oncol. 2013 Sep;24(9):2409-14. doi: 10.1093/annonc/mdt219. Epub 2013 Jun 20.
Pubmed: (View Article at PubMed) PMID:23788753
DOI: Full-text: DOI:10.1093/annonc/mdt219


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 AND METHODS: 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.

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CRRD Object Information
CRRD ID: 13506731
Created: 2018-02-08
Species: All species
Last Modified: 2018-02-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.