Aberrant localization of the neuronal class III beta-tubulin in astrocytomas - A marker for anaplastic potential

Background.-The class III beta -tubulin isotype (beta III) is widely regard ed as a neuronal marker in development and neoplasia. In previous work, we have shown that the expression of beta III in neuronal/neuroblastic tumors is differentiation dependent. In contrast, the aberrant localization of thi s isotype in certain nonneuronal neoplasms, such as epithelial neuroendocri ne lung tumors, is associated with anaplastic potential. Objective.-To test the generality of this observation, we investigated the immunoreactivity profile of beta III in astrocytomas. Design,Sixty archival, surgically excised astrocytomas (8 pilocytic astrocy tomas, WHO grade 1; 18 diffuse fibrillary astrocytomas, WHO grade 2; 4 anap lastic astrocytomas, WHO grade 3; and 30 glioblastomas, WHO grade 4), were studied by immunohistochemistry using anti-pill monoclonal (TuJ1) and polyc lonal antibodies. A monoclonal antibody to Ki-67 nuclear antigen (NC-MM1) w as used as a marker For cell proliferation. Antibodies to glial fibrillary acidic protein (GFAP) and BM89 synaptic vesicle antigen/synaptophysin were used as glial and neuronal markers, respectively. Results.-The beta III immunoreactivity was significantly greater in high-gr ade astrocytomas (anaplastic astrocytomas and glioblastomas; median labelin g index [MLI], 35%; interquartile range [IQR], 20%-47%) as compared with di ffuse fibrillary astrocytomas (MLI, 4%; IQR, 0.2%-21%) (P < .0001) and was rarely detectable in pilocytic astrocytomas (MLI, 0%; IQR, 0%-0.5%) (P < .0 001 vs high-grade astrocytomas; P < .01 vs diffuse fibrillary astrocytomas) . A highly significant, grade-dependent relationship was observed between < beta>III and Ki-67 labeling and malignancy, but this association was strong er for Ki-67 than for beta III (beta III, P < .006; Ki-67, P < .0001). Ther e was co-localization of beta III and GFAP in neoplastic astrocytes, but no BM89 synaptic vesicle antigen/synaptophysin staining was detected. Conclusions.-In the context of astrocytic gliomas, beta III immunoreactivit y is associated with an ascending gradient of malignancy and thus may be a useful ancillary diagnostic marker. However, the significance of pill-posit ive phenotypes in diffuse fibrillary astrocytomas with respect to prognosti c and predictive value requires further evaluation. Under certain neoplasti c conditions, pill expression is not neuron specific, calling For a cautiou s interpretation of pill-positive phenotypes in brain tumors.