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FGFR1 is associated with c‐MYC and proangiogenic molecules in metastatic renal cell carcinoma under anti‐angiogenic therapy
Author(s) -
Park Jee Young,
Kim PilJong,
Shin SuJin,
Lee JaeLyun,
Cho Yong Mee,
Go Heounjeong
Publication year - 2020
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14076
Subject(s) - fibroblast growth factor receptor 1 , immunohistochemistry , cancer research , angiogenesis , clear cell renal cell carcinoma , tissue microarray , receptor tyrosine kinase , renal cell carcinoma , metastasis , medicine , biology , cancer , fibroblast growth factor , receptor
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.