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


METHODS
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.
Katsetos
C D
CD
Section of Neurology/Research Laboratories, St Christopher's Hospital for Children, Erie Avenue at Front Street, Philadelphia, PA 19134, USA. Christos.D.Katsetos@drexel.edu
Del Valle
L
L
Geddes
J F
JF
Assimakopoulou
M
M
Legido
A
A
Boyd
J C
JC
Balin
B
B
Parikh
N A
NA
Maraziotis
T
T
de Chadarevian
J P
JP
Varakis
J N
JN
Matsas
R
R
Spano
A
A
Frankfurter
A
A
Herman
M M
MM
Khalili
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000737:chemistry* / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000737:chemistry* / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis / Q000276:immunology; D008875:Middle Aged; D016708:Synaptophysin / Q000032:analysis; D014404:Tubulin / Q000032:analysis* / Q000276:immunology
D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D016708:Synaptophysin; D014404:Tubulin