Aberrant localization of the neuronal class III beta-tubulin in astrocytomas

Arch Pathol Lab Med. 2001 May;125(5):613-24. doi: 10.1043/0003-9985(2001)125<0613:ALOTNC>2.0.CO;2.

Abstract

Background: The class III beta-tubulin isotype (betaIII) is widely regarded as a neuronal marker in development and neoplasia. In previous work, we have shown that the expression of betaIII 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 betaIII 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-betaIII 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 betaIII 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 betaIII and Ki-67 labeling and malignancy, but this association was stronger for Ki-67 than for betaIII (betaIII, P <.006; Ki-67, P <.0001). There was co-localization of betaIII and GFAP in neoplastic astrocytes, but no BM89 synaptic vesicle antigen/synaptophysin staining was detected.

Conclusions: In the context of astrocytic gliomas, betaIII immunoreactivity is associated with an ascending gradient of malignancy and thus may be a useful ancillary diagnostic marker. However, the significance of betaIII-positive phenotypes in diffuse fibrillary astrocytomas with respect to prognostic and predictive value requires further evaluation. Under certain neoplastic conditions, betaIII expression is not neuron specific, calling for a cautious interpretation of betaIII-positive phenotypes in brain tumors.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Astrocytoma / chemistry*
  • Astrocytoma / diagnosis*
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / chemistry*
  • Brain Neoplasms / diagnosis*
  • Child
  • Child, Preschool
  • Glial Fibrillary Acidic Protein / analysis
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / immunology
  • Middle Aged
  • Synaptophysin / analysis
  • Tubulin / analysis*
  • Tubulin / immunology

Substances

  • Biomarkers, Tumor
  • Glial Fibrillary Acidic Protein
  • Ki-67 Antigen
  • Synaptophysin
  • Tubulin