EGFR is frequently hyperexpressed in human malignant peripheral nerve sheath tumors (MPNST) and is preferentially localized in high grade areas

Abstract

21105 Background: MPNST are highly malignant Schwann cell neoplasms that are generally resistant to conventional radiation and chemotherapy. Mouse models and in vitro data suggest that epidermal growth factor receptor (EGFR) expression is implicated in malignant transformation of Schwann cells. Methods: MPNST samples from 52 patients were studied for EGFR, Ki67, neurofibromin, p53 and survivin expression by immunohistochemistry and for EGFR amplification by in situ hybridization. Results were correlated with clinical data. EGFR RNA were also quantified by RT-PCR in 20 other MPNST and 14 cutaneous neurofibroma samples. Results: Half of the patients had a neurofibromatosis type 1 (NF1), and their age was lower at diagnosis (19 versus 27 years, P=0.04). EGFR expression was detected in 86% of MPNST, and was more frequent in NF1 (95% versus 75%). The staining of tumor cells was heterogeneous in several cases, and closely associated with high grade, Ki67 high and p53 positive areas. MPNST expressed a higher level of EGFR transcripts than neurofibromas. The five year survival was 33%, and NF1 status was the only prognostic factor in multivariate analysis. Conclusion: Our data suggest that EGFR may become a target for new therapies in MPNST, in particular in NF1-associated MPNSTs. No significant financial relationships to disclose.