OTX1 and OTX2 expression correlates with the clinicopathologic classification of medulloblastomas

Talitha De Haas, Esmeralda Oussoren, Wieslawa Grajkowska, Marta Perek-Polnik, Mara Popovic, Lorna Zadravec-Zaletel, Marzia Perera, Giorgio Corte, Oliver Wirths, Peter Van Sluis, Torsten Pietsch, Dirk Troost, Frank Baas, Rogier Versteeg, Marcel Kool

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71 Citaten (Scopus)

Samenvatting

OTX1 and OTX2 are transcription factors with an essential role in the development of the cerebellum. We previously described a high OTX2 expression in medulloblastoma. Here, we analyzed amplification and mRNA expression of OTX1 and OTX2 in a series of human medulloblastomas. In addition, OTX2 protein expression was analyzed on tissue arrays. The OTX2 gene was amplified in the medulloblastoma cell line D425 and mRNA and protein data showed expression in 114 of 152 medulloblastomas (75%), but not in postnatal cerebellum. Northern blot (n = 10) and reverse transcriptase-polymerase chain reaction (n = 45) analyses demonstrated that virtually all medulloblastomas expressed OTX1, OTX2, or both. OTX2 mRNA expression correlated with a classic medulloblastoma histology (29 of 34 cases), whereas expression of OTX1 mRNA only was correlated with a nodular/desmoplastic histology (9 of 11 cases). Immunohistochemical analysis of a series of classic medulloblastomas detected OTX2 protein expression in 83 of 107 (78%) cases. The OTX2-positive tumors of this series were preferentially localized in the vermis of the cerebellum, whereas OTX2-negative tumors more frequently occurred in the hemispheres of the cerebellum. In addition, OTX2-positive tumors were mainly found in children, but OTX2-negative tumors occurred in 2 patient groups: very young patients (<5 years) and adults (>20 years). Nodular/desmoplastic medulloblastomas are thought to arise from the external granular layer (EGL). However, it is unclear whether classic medulloblastomas also originate from the EGL or from the ventricular matrix. Analysis of human fetal brain showed OTX2 protein expression in a small number of presumptive neuronal precursor cells of the EGL, but not in precursor cells of the ventricular matrix. Combined with data from rodents, our results therefore suggest that both nodular/desmoplastic and at least part of the classic medulloblastomas originate from cells of the EGL, albeit from different regions.

Originele taal-2Engels
Pagina's (van-tot)176-186
Aantal pagina's11
TijdschriftJournal of Neuropathology and Experimental Neurology
Volume65
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - feb. 2006
Extern gepubliceerdJa

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