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

Authors
 Jee Young Park 1 , Pil-Jong Kim 2 , Su-Jin Shin 3 , Jae-Lyun Lee 4 , Yong Mee Cho 5 , Heounjeong Go 5 
Citation
 HISTOPATHOLOGY, Vol.76(6) : 838-851, 2020-05 
Journal Title
 HISTOPATHOLOGY 
ISSN
 0309-0167 
Issue Date
2020-05
Keywords
angiogenesis ; c-MYC ; fibroblast growth factor receptor 1 ; metastatic clear cell renal cell carcinoma
Abstract
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. FGFR1high was an independent worse prognostic factor for overall (HR = 1.871, P = 0.032) and progression-free (HR = 1.976, P = 0.016) survival. 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 (P < 0.0001). FGFR1high /c-MYChigh 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.
Full Text
https://onlinelibrary.wiley.com/doi/full/10.1111/his.14076
DOI
10.1111/his.14076
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Shin, Su Jin(신수진) ORCID logo https://orcid.org/0000-0001-9114-8438
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180730
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