Prognostic and Therapeutic Utility of Variably Expressed Cell Surface
Receptors in Osteosarcoma
Abstract
Background: Six cell surface receptors, human epidermal growth factor
receptor (Her)-2, platelet-derived growth factor receptor (PDGFR)-β,
insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR),
c-Met, and vascular endothelial growth factor receptor (VEGFR)-3,
previously demonstrated variable expression across varying osteosarcoma
(OS) cell lines. The current study sought to validate previous
expression patterns and evaluate whether these receptors offer
prognostic and therapeutic value. Methods: Patient-derived OS samples (n
= 52) were labeled with antibodies to Her-2, PDGFR-β, IGF-1R, IR, c-Met,
and VEGFR-3. Expression was characterized using flow cytometry. The
geometric mean fluorescent intensity (geoMFI) for each receptor was
calculated relative to a negative control. The event-free survival (EFS)
and overall survival for patients with positive receptor expression were
estimated by the Kaplan-Meier method. Differences in hazard for EFS
event and overall survival event for patients with positive receptor
expression were assessed using the log-rank test. Results: All 6
receptors were variably expressed in the majority of cell lines. None of
the 6 receptors, were found to be significant predictors of EFS or
overall survival. The sum total number of positive receptors per cell
line also failed to predict EFS or overall survival. Conclusion: The six
cell surface receptors demonstrated variable expression across the
majority of patient-derived OS samples tested. While receptor expression
did not provide prognostic value, their consistent expression makes them
attractive targets for future therapeutic approaches.