Aberrant Localization of the Neuronal Class III b-Tubulin in Astrocytomas A Marker for Anaplastic Potential

Abstract

c Background.—The class III b-tubulin isotype (bIII) is widely regarded as a neuronal marker in development and neoplasia. In previous work, we have shown that the expression of bIII 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 bIII 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-bIII 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 bIII 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 bIII and Ki-67 labeling and malignancy, but this association was stronger for Ki-67 than for bIII (bIII, P , .006; Ki-67, P , .0001). There was co-localization of bIII and GFAP in neoplastic astrocytes, but no BM89 synaptic vesicle antigen/synaptophysin staining was detected. Conclusions.—In the context of astrocytic gliomas, bIII immunoreactivity is associated with an ascending gradient of malignancy and thus may be a useful ancillary diagnostic marker. However, the significance of bIII-positive phenotypes in diffuse fibrillary astrocytomas with respect to prognostic and predictive value requires further evaluation. Under certain neoplastic conditions, bIII expression is not neuron specific, calling for a cautious interpretation of bIII-positive phenotypes in brain tumors. (Arch Pathol Lab Med. 2001;125:613‐624)