Expression of ZIC family genes in meningiomas and other brain tumors

Jun Aruga,Minoru Hatayama,Naoki Yokota,Yayoi Nozaki,Yuri S Odaka

doi:10.1186/1471-2407-10-79

Jun Aruga, Minoru Hatayama + Show 3 more

Open Access

https://doi.org/10.1186/1471-2407-10-79

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Abstract

BackgroundZic zinc finger proteins are present in the developing rodent meninges and are required for cell proliferation and differentiation of meningeal progenitors. Although human ZIC genes are known to be molecular markers for medulloblastomas, their expression in meningioma has not been addressed to date.MethodsWe examined the mRNA and protein expression of human ZIC1, ZIC2, ZIC3, ZIC4 and ZIC5 genes in meningiomas in comparison to other brain tumors, using RT-PCR, analysis of published microarray data, and immunostaining.ResultsZIC1, ZIC2 and ZIC5 transcript levels in meningiomas were higher than those in whole brain or normal dura mater, whereas all five ZIC genes were abundantly expressed in medulloblastomas. The expression level of ZIC1 in public microarray data was greater in meningiomas classified as World Health Organization Grade II (atypical) than those classified as Grade I (benign). Immunoscreening using anti-ZIC antibodies revealed that 23 out of 23 meningioma cases were ZIC1/2/3/5-immunopositive. By comparison, nuclear staining by the anti-ZIC4 antibody was not observed in any meningioma case, but was strongly detected in all four medulloblastomas. ZIC-positive meningiomas included meningothelial, fibrous, transitional, and psammomatous histological subtypes. In normal meninges, ZIC-like immunoreactivities were detected in vimentin-expressing arachnoid cells both in human and mouse.ConclusionsZIC1, ZIC2, and ZIC5 are novel molecular markers for meningiomas whereas ZIC4 expression is highly selective for medulloblastomas. The pattern of ZIC expression in both of these tumor types may reflect the properties of the tissues from which the tumors are derived.

Highlights

Zinc finger protein of the cerebellum (Zic) zinc finger proteins are present in the developing rodent meninges and are required for cell proliferation and differentiation of meningeal progenitors
Expression of ZIC1-5 in various types of brain tumors We first examined the mRNA levels of the five ZIC genes in various types of brain tumors including astrocytoma, oligodendroglioma, glioblastoma, medulloblastoma, primitive neuroectodermal tumor, ganglioglioma, neurinoma, subependymoma, and meningioma (Figure 1, Table 1)
The mRNA levels of ZIC1, ZIC2 and ZIC5 were higher in meningioma than in dura mater

Summary

Introduction

Zic zinc finger proteins are present in the developing rodent meninges and are required for cell proliferation and differentiation of meningeal progenitors. Meningiomas are the most common type of benign intracranial brain tumor, with an annual incidence of approximately 2.3 to 6 per 100,000 persons [1]. They are classified into three World Health Organization (WHO) grades: benign (Grade I), atypical (Grade II), and malignant (Grade III) [1] based on the degree of anaplasia, number of mitoses, and presence of necrosis [1,3]. Mouse Zic proteins are present in the primitive meninx (meningeal cell precursors), and a deficiency of Zic or Zic1/Zic results in impaired proliferation and differentiation of meningeal precursors [4]. These findings led us to hypothesize that ZIC proteins are present in meningiomas

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