821P - VEGF and VEGFRs polymorphisms analysis in advanced renal cell carcinoma tissues: Is heterogeneity ever the answer?

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Renal Cell Cancer
Translational Research
Presenter Maristella Bianconi
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors M. Bianconi1, M. Scartozzi1, L. Faloppi1, A. Zizzi2, M. D'Anzeo1, M. Del Prete1, R. Giampieri1, L. Burattini1, R. Montironi2, S. Cascinu1
  • 1Clinica Di Oncologia Medica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT
  • 2Institute Of Pathological Anatomy, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT

Abstract

Aim

Metastatic renal cell carcinoma (mRCC) ever represented a challenge in patients' treatment, even with the new generation drugs. In fact there is a wide variability in the amount and duration of response among patients. Sunitinib a drug mainly targeting the angiogenic pathway, is commonly used in mRCC treatment. We previously reported how VEGF and VEGFRs SNPs could predict response to treatment with either sunitinib or pazopanib. Tumour heterogeinity and its possible correlation with response is matter of debate in mRCC. The aim of our study is to assess the expression of VEGF and VEGFRs polymorphisms in tumour, metastatic and normal renal tissues.

Methods

We enrolled 123 patients treated at our Institution. We collected histologic samples of tumour, metastatic and normal renal tissue of 84 patients with mRCC treated with first-line sunitinib. For 61 patients samples of tumour, metastatic and normal renal tissue were available. Histologic samples were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Polymorphisms were correlated with PFS and OS. We then analysed concordance in SPNs expression among tissues.

Results

The VEGF A rs833061 resulted significant in PFS (C > T, 17 vs 4 months; p<0.0001) and OS (C>T, 38 vs 10 months; p<0.0001). The VEGF A rs699947 was significant for PFS (A>C, 18 vs 4 months; p = 0.0001) and OS (A > C, 37 vs 16 months; p<0.0001). The VEGF A rs2010963 was significant in PFS (G>C, 18 2 months; p = 0.0001) and OS (G > C, 36 vs 9 months; p = 0.0045). The VEGR3 rs6877011 was significant in PFS (C > G, 12 vs 4 months; p = 0.0075) and OS (C > G, 36 vs 17 months; p = 0.0001). 59 out of 61 patients presented concordance between tumour, metastatic and normal renal tissue (97%).

Conclusions

Preliminary data from our analysis show how angiogenic polymorphisms are significantly correlated with either PFS and OS. These polymorphisms genotypes are preserved between tumour, its metastatic sites and the normal renal tissue. Further analyses will be presented at the meeting.

Disclosure

All authors have declared no conflicts of interest.