Expression of Ras signaling pathway proteins and developmental factors in peripheral nerve sheath tumors of patients with neurofibromatosis type 1.

Purpose: To characterize expression of factors relevant for Ras signaling and developmental factors in a large series of peripheral nerve sheath tumors (PNST) obtained from patients with neurofibromatosis type 1 (NF1).

Materials and methods: Tissue micro-array technique was applied to study 520 PNST of 385 NF1 patients by immunohistochemistry for mTor, Rho, phosphorylated MEK, Pax7, Sox9, and periaxin expression. PNST comprised cutaneous neurofibroma (CNF) (n = 114), diffuse neurofibroma (DNF) (n = 109), diffuse plexiform neurofibroma (DPNF) (n = 108), plexiform neurofibroma (PNF) (n = 110), and malignant PNST (MPNST) (n = 22).

Results: All proteins examined showed highest expression levels/highest frequency of expression in MPNST. Benign PNF with potential for malignant dedifferentiation expressed mTor, phosphorylated MEK, Sox9, and periaxin significantly higher/more frequently than other benign neurofibroma subtypes.

Conclusion: In NF1-associated PNST, expression of proteins involved in Ras-signaling and development is upregulated not only in MPNST, but also in benign PNF with the potential for malignant dedifferentiation. The differences in protein expression may provide clues for understanding the therapeutic effects of substances applied for reduction of PNST in NF1.