Localization of the neuronal class III β-tubulin in oligodendrogliomas: Comparison with Ki-67 proliferative index and 1p/19q status

Abstract

The class III β-tubulin isotype (βIII) is widely regarded as a neuronal marker in development and neoplasia. Whereas the expression of βIII in neuronal/neuroblastic tumors is differentiation-dependent, the aberrant expression of this cytoskeletal protein in astrocytomas is associated with an ascending gradient of malignancy. To test the generality of this observation we have compared the immunoreactivity (IR) profiles of the βIII isotype with the Ki-67 nuclear antigen proliferative index in 41 archival, surgically excised oligodendrogliomas (32 classical [WHO grade II] and 9 anaplastic [WHO grade Ill]). Seventeen of 41 tumors were examined by quantitative microsatellite analysis for loss of lp and/or 19q. Minimal deletion regions were defined on 1p (D1S468, D1S214) and 19q (D19S408, D19S867). Three of 10 classical oligodendrogliomas had combined lp/19q loss, while 2 exhibited loss of either lp or 19q. Three of 7 anaplastic tumors had combined lp/19q loss. βIII IR was present in all tumors, but was significantly greater in the anaplastic (median labeling index [MLI] 61%, interquartile range [IQR] 55%-64%) as compared with the classical variants (MLI, 19%, IQR, 11-36%) (p > 0.0001). A highly significant relationship was found to exist between βIII and Ki-67 LIs (βIII, p < 0.0001 and Ki-67, p < 0.0001, r = 0.809). βIII localization delineated hitherto understated unipolar or bipolar tumor phenotypes with growth cones and leading cell processes resembling migrating oligodendrocyte progenitor cells. Codistribution of βIII and GFAP IR was present in "gliofibrillary" tumor areas. Synaptophysin IR was detected in rare tumor cells (mean LI, 0.7%), and only in 4/41 samples (10%), denoting a lack of relationship between βIII and synaptophysin expression. No significant differences in βIII LIs were observed in tumors with lp and/or 19q loss as compared to those with lp/19q intact status. Increased βIII IR in oligodendrogliomas is associated with an ascending degree of malignancy and thus is a potentially useful tumor marker. However, the significance of high βIII Lis in low-grade oligodendrogliomas with respect to prognostic and predictive value requires further evaluation. Class III β-tubulin expression in oligodendrogliomas should not be construed as a priori evidence of divergent neuronal differentiation.