Neurofibromin immunoexpression in nerve sheath tumors from nf1 patients

The aim of the present study was to assess the differential immunoexpression of neurofibromin in benign and malignant peripheral nerve sheath tumors (PNST) from Neurofibromatosis type l (NF1) patients. Two polyclonal antibodies raised against peptides corresponding to residues 2798-2818 and 509-528 of the NF1 gene product, that specifically recognize the 250 kd NF1 gene product were used. Using enzymatic antigen enhancement these antibodies were applied to formalin-fixed, paraffin-embedded tissue sections. Neurofibromin immunoreactivity was seen in normal dorsal root ganglia, Schwärm cells, keratinocytes, melanocytes, CNS neurons and oligodendrocytes. 38 PNST from 25 NF1 patients were examined. 7/7 malignant PNST immunoexpressed neurofibromin, as detected with both antibodies. 26β1 benign neurofibromas were also positive while immunoreactivity was not detected in 5 benign tumors. Double immunolabelling with S-100 demonstrated neurofibromin within Schwann cells. Immunoabsorption of primary antibodies with corresponding peptides eliminated labelling. Our results negate the concept that malignancy within NF1 tumors is a consequence of neurofibromin deficiency and thus raises additional questions regarding the role of this molecule in the pathogenesis of NF1.