Alpha-synuclein expression in central nervous system tumors showing neuronal or mixed neuronal/glial differentiation

Alpha-synuclein (alpha-synuclein) is a member of a family of cytoplasmic pr oteins found predominantly and abundantly in the brain, and concentrated in pre-synaptic nerve terminals. near vesicles. We hypothesized that an antib ody to alpha-synuclein could be a useful marker of neuronal differentiation in central nervous system (CNS) tumors. Twenty tumors known to have neuron al or mixed neuronal/glial differentiation (11 gangliogliomas. 2 anaplastic gangliogliomas, 5 gangliocytomas, and 2 ganglioneuroblastomas), 5 central neurocytomas, and 1 dysembryoplastic neuroepithelial tumor (DNET) were immu nostained with a mouse monoclonal antibody raised against human alpha-synuc lein. Intense cytoplasmic staining. in some instances extending into the pe rikarya. was seen in 6 of 11 gangliogliomas. 7 of? anaplastic ganglioglioma s. and 2 of 2 ganglioneuroblastomas. Alpha-synuclein-positive cells were us ually large in size, resembled dysmorphic neurons, and were variably immuno reactive for anti-neurofilament and/or anti-synaptophysin antibodies. In co ntrast, central neurocytomas, gangliocytomas, and the DNET were negative fo r cytoplasmic alpha-synuclein expression. Our findings indicate that alpha- synuclein is expressed within the neuronal component of mixed tumors of the CNS displaying more than 1 histophenotype, and/or showing different degree s of anaplasia. Based on currently available data, we conclude that cytopla smic alpha-synuclein expression is a marker of maturing neurons in these tu mors.