HUMAN NEOPLASTIC SCHWANN-CELLS - CHANGES IN THE EXPRESSION OF NEUROTROPHINS AND THEIR LOW-AFFINITY RECEPTOR P75

Neurotrophins are known to influence Schwann cells during development and to promote peripheral nerve regeneration after axonal damage. In n eoplastic conditions, Schwann cells from experimentally-induced schwan nomas appear to retain their responsiveness to nerve growth factor (NG F), although the role of neurotrophins in the neoplastic process is po orly understood. In this study, human neoplastic Schwann cells (five c ases of acoustic schwannoma and two cases of malignant peripheral nerv e sheath tumours [MPNST]) were investigated for the expression in situ of molecules of the neurotrophin system. In particular, we studied th e 75 kDa low-affinity receptor (p75) and the mRNA for its ligands, NGF and neurotrophin-3 (NT-3). By immunohistochemistry, the p75 receptor was found to be present at high levels in Schwann cells from acoustic schwannomas, whereas it was very weak or absent in MPNST. Messenger RN A for NGF and NT-3 was detected by reverse transcriptase in situ polym erase chain reaction technique and showed the same fluctuation of p75, being up-regulated in acoustic schwannomas and very weak or absent in MPNST. In normal non-neoplastic tissue, no detectable amounts of eith er ligand or receptor were observed. Our results indicate that changes in the expression of neurotrophins and their p75 receptor occurred du ring the neoplastic transformation of Schwann cells. In benign schwann omas, such changes are likely to reflect the loss of axonal contact, w hile in MPNST they may be related to a complete derangement; of cell m achinery in the tumour cells.