A possible paracrine hedgehog signalling pathway in neurofibromas from patients with neurofibromatosis type 1.

Abstract

Hedgehogs (Hhs) and their receptors are involved in organ development as well as in tumorigenesis observed in basal cell carcinoma. Among Hhs, Desert hedgehog secreted from Schwann cells mediates the formation of peripheral nerve sheaths. However, there has been no study on the role of Hhs and their receptors in tumorigenesis of neurofibromas in neurofibromatosis type 1 (NF1). To clarify the expression and localization of Hhs and their receptors in neurofibromas of NF1 patients. Expression of Hhs and their receptors was studied by immunohistochemistry using neurofibromas from NF1 patients and control normal skin samples. In neurofibromas, CD57-positive tumour cells with delicate elongated processes were positive for the receptor PTCH2. Perineurial cells of involved nerves within neurofibromas as well as those of normal cutaneous nerves expressed Indian hedgehog and Sonic hedgehog. Schwann cells of normal cutaneous nerves were positive for PTCH2. Our study suggests that a paracrine Hh signalling pathway may be involved in tumorigenesis of neurofibromas in NF1.