EXPRESSION OF NEUROFIBROMATOSIS-2 PROTEIN IN HUMAN BRAIN-TUMORS - AN IMMUNOHISTOCHEMICAL STUDY

The neurofibromatosis 2 (NF2) gene-encoded protein, named merlin, may function as a molecular linkage connecting cytoskeleton and plasma mem brane. Merlin is thought to play a crucial role as a tumor suppressor not only in hereditary NF2-related tumors, but also in sporadic tumors such as schwannomas, meningiomas and gliomas. Using a merlin-expressi on vector system, we raised specific antiserum against merlin. We obse rved the intracellular distribution of merlin in cultured glioma cells , and further investigated merlin expression in 116 human brain tumors . Immunofluorescence microscopy revealed that merlin was localized ben eath the cell membrane and concentrated at cell-to-cell adhesion sites , where actin filaments are densely associated with plasma membrane. B y immunohistochemistry, none of the schwannomas from either NF2 patien ts or sporadic cases showed any immunoreactivity, while normal Schwann cells of cranial nerves were immunopositive. In meningiomas, merlin e xpression was frequently seen in the meningothelial subtype (8/10, 80% ), but no expression could be detected in either the fibrous or the tr ansitional variant. Most normal astrocytes were negative; however, rea ctive astrocytes often expressed merlin. Glioblastomas and anaplastic astrocytomas were found to be strongly positive, and focal positive st aining was observed in fibrillary and pilocytic astrocytomas. Thus, th e loss of merlin appears to be integral to schwannoma formation and th e differential pathogenesis of meningioma subtypes. However, merlin al terations do not appear to play a critical role in either the tumorige nesis or malignant transformation of neoplastic astrocytes.