Abstract
Purpose :
Embryonal Rhabdomyosarcoma (RMS) is the most common sarcoma of childhood and about 10% arise in the orbit. Receptor tyrosine kinases (RTKs) inhibitors are novel, prognosis-improving agents in many cancers. Their role in orbital rhabdomyosarcoma remains to be explored.
In the present study, expression of receptor tyrosine kinases and their clinical relevance in orbital RMS has been explored.
Methods :
Eighteen histopathologically confirmed orbital rhabdomyosarcoma cases and 5 normal skeletal muscle controls were included in this prospective observational study. Comprehensive qPCR gene expression profiles of 12 RTKs (VEGFR1, VEGFR2 ,VEGFR3, EGFR1,EGFR2, EGFR3, EGFR4, AXL, MET, IGF2R, FGFR1 and FGFR2) in all the cases and controls was undertaken. Patients were followed up for 12 months (mean 8.6 ±6 months). Kaplan-Meier plots and Spearman's rank correlation tests were applied to analyse the data.
Results :
Of the 18 embryonal rhabdomyosarcomas cases 70-94% showed mRNA overexpression of MET, EGFR4 AXL and FGFR2. Overexpression of FGFR1, EGFR3, VEGFR2, EGFR2 and IGF2R was seen in 50-70% ER cases. Down-regulation of VEGFR1, VEGFR3 and EGFR1 was seen in 65-85% of the rhabdomyosarcoma patients. Of the 12 markers analyzed overexpression of MET gene was significantly associated with worst disease free survival (P=0.008) in patients of embryonal rhabdomyosarcoma.
A significant and direct correlation was observed between MET and VEGFR2 (P=0.002), AXL (P=0.0001) and FGFR1 (P=0.05) gene expression.
Conclusions :
Overexpression of MET gene could be a useful biomarker for identifying high-risk orbital rhabdomyosarcoma patients.Its overexpression was significantly associated with VEGFR2, AXL, FGFR1. Therefore the effect of a multi-kinase inhibitor targeting MET, AXL, FGFR1 and VEGFR2 could be a potential therapeutic target in the management of embryonal rhabdomyosarcomas. In-vitro studies are recommended to validate these results.
This is a 2020 ARVO Annual Meeting abstract.