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

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).

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 (p<0.0001). FGFR1high /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.

FGFR might act as negative predictive factor of responsiveness to VEGFR-TKIs. FGFR1 and c-MYC may involve in tumour angiogenesis in metastatic CCRCC.

Histopathology. 2020 Jan 28 [Epub ahead of print]

Jee Young Park, Pil-Jong Kim, Su-Jin Shin, Jae-Lyun Lee, Yong Mee Cho, Heounjeong Go

Department of Pathology, Kyungpook National University Medical Centre, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Biomedical Knowledge Engineering Laboratory, Seoul National University School of Dentistry and Dental Research Institute, Seoul, Republic of Korea., Department of Pathology, Gangnam Severance Hospital, Seoul, Republic of Korea., Department of Oncology, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea., Department of Pathology, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Republic of Korea.