Expression of ZIC family genes in meningiomas and other brain tumors.
BACKGROUND
Zic 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.


METHODS
We 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.


RESULTS
ZIC1, 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.


CONCLUSIONS
ZIC1, 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.
Aruga
Jun
J
Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan. jaruga@brain.riken.jp
Nozaki
Yayoi
Y
Hatayama
Minoru
M
Odaka
Yuri S
YS
Yokota
Naoki
N
D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008579:Meningioma / Q000175:diagnosis / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000096:biosynthesis; D013234:Stem Cells; D014157:Transcription Factors / Q000096:biosynthesis; D014746:Vimentin / Q000096:biosynthesis; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D014746:Vimentin; C492123:ZIC1 protein, human; C491812:ZIC2 protein, human; C485965:ZIC5 protein, human