Expression of 'drugable' tyrosine kinase receptors in malignant peripheral nerve sheath tumour: potential molecular therapeutic targets for a chemoresistant cancer.

AIMS

Novel therapeutic approaches for the treatment of malignant peripheral nerve sheath tumors (MPNSTs) are critically needed. Tyrosine kinase receptors are commonly deregulated in cancer and constitute attractive targets. We assessed the protein expression level of a panel of ‘drugable’ TKRs in a relatively large cohort of human plexiform and MPNST surgical specimens.

METHODS AND RESULTS

Immunohistochemistry for HER2, PDGFRA, PDGFRB, KIT, IGF-1R, MET, and AXL was performed on an MPNST tissue microarray, yielding data from 99 tumors (plexiform/atypical neurofibroma = 26 and MPNST =73). PDGFRA, PDGFRB, MET, IGFR, and AXL were found to be highly expressed in human MPNST and all but AXL were significantly higher in MPNST as compared to neurofibroma. No HER2 expression was found. KIT expression in tumor cells was uncommon, but highlighted mast intratumoral cells in both neurofibroma and MPNST.

CONCLUSIONS

Several TKRs were overexpressed in MPNSTs, exhibiting tumor-to-tumor heterogeneity. When designing future MPNST clinical trials, pre-treatment molecular analysis may help in ‘smart’ patient selection. Furthermore, utilizing single compounds blocking multiple TKRs or therapeutic combinations could constitute a superior anti-MPNST treatment approach.