IMMUNOHISTOCHEMICAL DETECTION OF SCHWANNOMIN AND NEUROFIBROMIN IN VESTIBULAR SCHWANNOMAS, EPENDYMOMAS AND MENINGIOMAS

In addition to schwannomas, patients with neurofibromatosis type 2 (NF 2) frequently develop meningiomas and occasionally, ependymomas. Using DNA and protein analyses, we have shown NF2 gene mutations and lack o f the gene product schwannomin in 29 schwannomas, 10 meningiomas, and in 7 ependymomas. We have raised antibodies (ABs) to peptides from the C-terminal (5990-AB) and N-terminal (5991-AB) domains of schwannomin. The ABs specifically detected a 65 kDa protein in a Schwann cell line and recognized schwannomin in the cytoplasm of Schwann cells (SCH), p erineurial cells, and vestibular ganglion neurons. None of the 29 schw annomas were stained by the 5990-AB. Only 4 schwannomas were stained b y the 5991-AB, indicating that most truncated schwannomins were unstab le or not expressed in schwannomas. Seven of 10 meningiomas, including 3 tumors from NF2 patients, were not stained by either 5990-AB or 599 1-AB. Only 2 of 7 ependymomas lacked schwannomin. Complete lack of sch wannomin in these tumors supports a tumor suppressor function for schw annomin in some meningiomas and ependymomas. All tumors showed stainin g with an antibody to a C-terminal peptide of neurofibromin, confirmin g that full-length neurofibromin is present in these vestibular schwan nomas, meningiomas, and ependymomas. The presence of schwannomin in so me meningiomas and in the majority of ependymomas indicates that addit ional genes are likely to play a role in tumorigenesis of these tumors .