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

Abstract

Background. - The class III β-tubulin isotype (βIII) is widely regarded as a neuronal marker in development and neoplasia. In previous work, we have shown that the expression of βIII in neuronal/neuroblastic tumors is differentiation dependent. In contrast, the aberrant localization of this isotype in certain nonneuronal neoplasms, such as epithelial neuroendocrine lung tumors, is associated with anaplastic potential. Objective. - To test the generality of this observation, we investigated the immunoreactivity profile of βIII in astrocytomas. Design. - Sixty archival, surgically excised astrocytomas (8 pilocytic astrocytomas, WHO grade 1; 18 diffuse fibrillary astrocytomas, WHO grade 2; 4 anaplastic astrocytomas, WHO grade 3; and 30 glioblastomas, WHO grade 4), were studied by immunohistochemistry using anti-βIII monoclonal (TuJ1) and polyclonal antibodies. A monoclonal antibody to Ki-67 nuclear antigen (NC-MM1) was 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 βIII immunoreactivity was significantly greater in high-grade astrocytomas (anaplastic astrocytomas and glioblastomas; median labeling index [MLI], 35%; interquartile range [IQR], 20%-47%) as compared with diffuse fibrillary astrocytomas (MLI, 4%; IQR, 0.2%-21%) (P < .0001) and was rarely detectable in pilocytic astrocytomas (MLI, 0%; IQR, 0%-0.5%) (P < .0001 vs high-grade astrocytomas; P < .01 vs diffuse fibrillary astrocytomas). A highly significant, grade-dependent relationship was observed between βIII and Ki-67 labeling and malignancy, but this association was stronger for Ki-67 than for βIII (βIII, P < .006; Ki-67, P