Angiogenic profile and pathological features in the prediction of clinical outcome of advanced renal cell carcinoma patients receiving sunitinib.

Abstract

458 Background: Metastatic renal cell carcinoma (mRCC) ever represented a challenge in patients’ treatment, there is a wide variability in the amount and duration of response among patients. It has been previously reported how VEGF and VEGFRs SNPs could predict response to treatment with sunitinib. Tumour heterogeinity is a matter of debate in mRCC. The aim of our study is to assess if pathological features and the expression of VEGF and VEGFRs polymorphisms in tumour, metastatic, and normal renal tissues could have a role in patients’ treatment and prognosis. Methods: We enrolled 123 patients treated at our institution. We collected histologic samples of tumour, metastatic, and normal renal tissue of 92 patients with mRCC treated with first-line sunitinib. For 21 patients, all three tissues were available. A pathological revision was conducted evaluating: granular cells percentage, grading, necrosis, regressive and sarcomatoid areas, and vascularization pattern. Histologic samples were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Polymorphisms were correlated with pathological features and PFS and OS. We then analysed concordance in SPNs expression among tissues. Results: VEGF A rs833061, VEGF A rs699947, VEGF A rs2010963, and VEGR3 rs6877011 were confirmed as significant SNPs in PFS. 19 out of 21 patients presented concordance among tissues polymorphisms expression (97%). The presence of a G allele in the rs6877011 seems to correlate with a higher percentage of granular cells. The presence of C allele in rs2010963 correlates with an alterated vascularazation. Conclusions: A preliminary analysis of our data shows the predictive and prognostic value of angiogenic polymorphisms and their concordance in tumoral, metastatic, and normal tissue. Furthermore, they are correlated with the percentage of granular cells and the vascular architecture, with possible predictive and prognostic significance. Further data will be presented at the meeting.