FGFR1 is associated with c‐MYC and proangiogenic molecules in metastatic renal cell carcinoma under anti‐angiogenic therapy
- 28 January 2020
- journal article
- research article
- Published by Wiley in Histopathology
- Vol. 76 (6), 838-851
- https://doi.org/10.1111/his.14076
Abstract
Aims This study aimed to investigate the clinicopathologic significance of FGFR1 and c‐MYC expression, particularly in relationship to angiogenesis in clear cell renal cell carcinoma (CCRCC). Methods and results Immunohistochemistry and fluorescence in situ hybridization 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 tumoural vascular density (TVD) were analysed. The mRNA expression and TVD of 533 CCRCCs in the 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. FGFR1high was an independent worse prognostic factor for overall (HR=1.871, p=0.032) and progression‐free (HR=1.976, p=0.016) survivals. FGFR1high was significantly related to VEGFR‐TKI responsiveness (p=0.011). The presence of FGFR1high/c‐MYChigh showed a positive correlation with proangiogenic markers, including VEGF (p=0.018) and HIF‐1α (phigh/c‐MYChigh tumours showed higher TVDs along with higher VEGFR2 and PDGFRβ 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 FGFR might act as negative predictive factor of responsiveness to VEGFR‐TKIs. FGFR1 and c‐MYC may involve in tumour angiogenesis in metastatic CCRCC.Keywords
Funding Information
- Asan Institute for Life Sciences, Asan Medical Center (2018‐800)
- National Research Foundation of Korea (2018R1C1B6007360)
This publication has 35 references indexed in Scilit:
- The impact of FGFR1 and FRS2α expression on sorafenib treatment in metastatic renal cell carcinomaBMC Cancer, 2015
- Personalized therapy on the horizon for squamous cell carcinoma of the lungLung Cancer, 2013
- Phase I Study of Dovitinib (TKI258), an Oral FGFR, VEGFR, and PDGFR Inhibitor, in Advanced or Metastatic Renal Cell CarcinomaClinical Cancer Research, 2013
- Targeting FGFR/PDGFR/VEGFR Impairs Tumor Growth, Angiogenesis, and Metastasis by Effects on Tumor Cells, Endothelial Cells, and Pericytes in Pancreatic CancerMolecular Cancer Therapeutics, 2011
- Overexpression of fibroblast growth factor receptors FGFR1 and FGFR2 in renal cell carcinomaScandinavian Journal of Urology and Nephrology, 2011
- Resistance to targeted therapy in renal-cell carcinomaThe Lancet Oncology, 2009
- Vascular endothelial growth factor‐targeted therapy in metastatic renal cell carcinomaCancer, 2009
- Sustained regression of tumors upon MYC inactivation requires p53 or thrombospondin-1 to reverse the angiogenic switchProceedings of the National Academy of Sciences of the United States of America, 2006
- Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumorsCancer Cell, 2005
- Conditionally MYC:insights from novel transgenic modelsCancer Letters, 2005