Giant cell glioblastoma and pleomorphic xanthoastrocytoma show different immunohistochemical profiles for neuronal antigens and p53 but share reactivity for class III [beta]-tubulin

Archives of Pathology & Laboratory Medicine, Sep 2003 by Martinez-Diaz, Hilda, Kleinschmidt-DeMasters, B K, Powell, Suzanne Z, Yachnis, Anthony T

* Context.-Giant cell glioblastoma multiforme (GCGBM) and pleomorphic xanthoastrocytoma (PXA) are clinically, radiographically, and histologically distinct tumors of the central nervous system. However, they share features of gross circumscription, reticulin deposition, lymphocytic infiltrates, and prominent populations of tumor giant cells. Neuronal antigens have been detected in the neoplastic cells of PXAs, but to our knowledge have not been studied previously in GCGBMs. While TP53 is mutated in most GCGBMs, a feature usually paralleled by strong immunostaining of the protein, the expression pattern of PXAs has not been extensively studied.

Objectives.-To compare the immunoprofiles of GCGBM and PXA with regard to neuronal antigens and p53 and to evaluate the potential diagnostic utility of such a panel.

Design.-Archival paraffin sections of 9 GCGBMs and 9 PXAs were immunostained for class III [beta]-tubulin, neuronal nuclear antigen, neurofilament protein, synaptophysin, glial fibrillary acidic protein, and p53.

Results.-Giant cell glioblastomas were strongly immunoreactive for class III [beta]-tubulin and glial fibrillary acidic protein, but showed only rare staining for the other neuronal polypeptides. In contrast, PXAs usually showed at least focal staining of individual tumor cells for most of the neuronal antigens tested. Tubulin was strongly positive in tumor giant cells and in smaller neoplastic cells of both tumor types. Double-immunolabeling revealed distinct populations of tumor cells that expressed either glial fibrillary acidic protein or tubulin and dual-labeling of individual cells in GCGBM and PXA. Strong p53 staining was observed in many tumor cells in 5 of 8 GCGBMs tested, while staining for this antigen was negative or focally positive in 6 of 8 PXAs examined.

Conclusions.-Giant cell glioblastoma multiforme and PXA show distinct patterns of immunoreactivity for neuronal antigens and p53 that may be useful diagnostically in difficult cases or in limited samples. These results provide further evidence of neuronal antigen expression by PXA.

The giant cell variant of glioblastoma multiforme (GCGBM) accounts for about 1% of primary brain tumors and 5% of glioblastomas (GBMs).1 Compared to more typical forms of GBM, the giant cell variant has a wider age range (with more younger individuals affected), is better circumscribed, and is believed to have a slightly better prognosis than more typical GBMs.1,2 Histologically, the most striking feature of this tumor is the presence of abundant, bizarre-appearing ("monstrocellular") tumor giant cells, many of which are multinucleated. Recent molecular and genetic analyses have revealed that GCGBM occupies an intermediate position between primary (de novo) GBM and the so-called secondary GBM, which is believed to arise from sequential anaplastic transformation of lower grade tumors.3-5 Like the primary GBM, GCGBMs appear to arise de novo, have a short clinical history, and have mutations of the PTEN/MMAC-1 gene in about one third of cases.5 However, TP53 gene mutations have been demonstrated in 75% to 90% of GCGBMs, while EGFR amplification is rare in these tumors, features that are different from primary GBM.3 Frequent TP53 mutations and the lower age at diagnosis are features shared by GCGBM and secondary GBM. While the giant cell variant has been reported to have a better prognosis than more conventional GBMs,6-9 the reasons for this difference are unknown and may relate to factors such as patient age (ie, the increased proportion of younger patients with GCGBM) and the possible inclusion of some pleomorphic xanthoastrocytomas (PXAs) in earlier clinicopathologic studies of GCGBM.

Pleomorphic xanthoastrocytoma is a primary neoplasm of the central nervous system (CNS) that was originally described by Kepes and colleagues.10-12 In contrast to the GCGBM, PXA is usually superficially located, has a predilection for the temporal lobe, and characteristically affects adolescents and young adults, who often present with a history of intractable seizures. Imaging studies usually reveal a large, well-circumscribed mass with cystic and solid components or a cyst with a mural nodule.13-16 Although favorable patient outcomes have been achieved with complete surgical excision, some of these tumors have followed a more aggressive course.12,17,18

Neuronal antigens have been identified in the pleomorphic tumor cell population of PXA,19-21 but they have not been analyzed previously in GCGBM. Class III [beta]-tubulin ([beta]III) is expressed during the earliest stages of neuronal differentiation and is confined to neurons and their processes in the adult.22-24 Detection of [beta]III using the monoclonal antibody TuJ1 has been widely used in the past as evidence of neuronal lineage in a variety of experimental systems. This tubulin isotype has been identified in a variety of nonglial CNS tumors,25-27 as well as in some non-CNS tumors28 and cell lines.29 Recently, [beta]III-like immunoreactivity has also been demonstrated in diffuse astrocytomas30 (including GBMs30-32) and in oligodendrogliomas.32,33 Two of these studies suggested that [beta]III expression correlated with greater malignant potential.30-33 However, in a recent study of 40 PXAs, Giannini et al21 identified [beta]III immunoreactivity in 73% of cases, and there was no apparent relationship between [beta]III expression and more aggressive behavior in PXAs. To our knowledge, the pattern of [beta]III expression in GCGBM has not been reported to date.