FGFR1 is associated with c-MYC and proangiogenic molecules in metastatic renal cell carcinoma under anti-angiogenic therapy.

AIMS:This study aimed to investigate the clinicopathological significance of FGFR1 and c-MYC expression, particularly in relation to angiogenesis in clear cell renal cell carcinoma (CCRCC). METHODS AND RESULTS:Immunohistochemistry and fluorescence in-situ hybridisation were conducted with tissue microarrays from 91 metastatic CCRCC patients who received VEGF receptor tyrosine kinase inhibitors (VEGFR-TKIs). The expression of angiogenic molecules, FGFR1 and c-MYC, and tumoral vascular density (TVD) and mRNA expression and TVD of 533 CCRCCs in The Cancer Genome Atlas (TCGA) were analysed. FGFR1, pFGFR1 and c-MYC expression was observed in 29.1, 74.4 and 30.8% of tumours, respectively. FGFR1^high was an independent worse prognostic factor for overall (HR = 1.871, P = 0.032) and progression-free (HR = 1.976, P = 0.016) survival. FGFR1^high was significantly related to VEGFR-TKI responsiveness (P = 0.011). The presence of FGFR1^high /c-MYC^high showed a positive correlation with proangiogenic markers, including VEGF (P = 0.018) and HIF-1α (P < 0.0001). FGFR1^high /c-MYC^high tumours showed higher TVDs together with higher VEGFR2 and PDGFR-β expression (both P < 0.0001). FGFR1 and c-MYC expression was also positively correlated with the expression of hypoxia-related and proangiogenic-related genes in the TCGA data. CONCLUSIONS:FGFR1 and c-MYC may be involved in tumour angiogenesis and FGFR1 may represent a promising therapeutic target in metastatic CCRCC.

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