Immunoexpression of neurofibromin, S-100 protein, and Leu-7 and mutation analysis of the NF1 gene at codon 1423 in osteofibrous dysplasia

The NF1 (neurofibromatosis type 1, or von Recklinghausen disease) gene, is a tumor-suppressor gene, and its product, neurofibromin, down-regulates ras protein by its guanosine triphosphatase-activating protein (GAP)-related d omain. Osteofibrous dysplasia (OFD) is characterized by fibroblast-like spi ndle cells and osseous tissue and is generally seen in the tibia or fibula during childhood. The precise nature of OFD remains controversial. Cosegreg ations of OFD and NF1 have been reported, and it has been surmised that OFD is associated with the NF1 gene. We studied the expressions of NF1 gene pr oduct (neurofibromin) and so-called Schwann cell markers (S-100 protein, Le u-7) in 17 cases of OFT) immunohistochemically. Ten cases of fibrous dyspla sia (FD) were also used for the purpose of comparison. Five OFD and 7 FD ca ses were analyzed for NF1 gene mutation at codon 1423, which is a GAP-relat ed domain, by single-strand conformation polymorphism. Fibroblast-like cell s of OFT) showed the expression of neurofibromin (5 of 17), S-100 protein ( 9 of 17), and Leu-7 (5 of 17), and those of ED did not show these expressio ns, with the exception of I case that showed Leu-7 expression. Regarding th e OFT) cases, significant correspondence was found between cases showing ex pression of neurofibromin and S-100 protein, between cases showing expressi on of neurofibromin and Leu-7, and between cases showing expression of S-10 0 protein and Leu-7 (P <.01). NF1 gene mutation at codon 1423 was not detec ted in either the OFT) (0 of 5) or FD (0 of 7) cases. These results seem to suggest the possible involvement of neurofibromin in the development of OF D, which is associated with the expression of Schwann cell markers (S-100 p rotein and Leu-7). Furthermore, NF1 gene mutation at codon 1423 did not see m to be related to OFD. HUM PATHOL 32: 1245-1251. Copyright (C) 2001 by W.B . Saunders Company.