TRANSTHYRETIN EXPRESSION IN MEDULLOBLASTOMAS AND MEDULLOBLASTOMA CELL-LINES

Transthyretin is a protein crucial to the transport of lipophilic mole cules such as thyroid hormones and retinoids. In. the central nervous system, large amounts of transthyretin are synthesized by the choroid plexus and are secreted into the cerebrospinal fluid. The choroid plex us is the only site of transthyretin synthesis in the brain, Transthyr etin is expressed by most benign and malignant choroid plexus tumours while gliomas and meningiomas do not express transthyretin, Other majo r sites of transthyretin synthesis are the retinal pigment epithelium and hepatocytes. Medulloblastoma is the prototypical primitive neuroec todermal tumour of the cerebellum and can show multiple lines of diffe rentiation, including the expression of retinal markers, In this study , we examined transthyretin expression both at the RNA and protein lev el in four medulloblastomas and six medulloblastoma cell lines using N orthern and Western blot analysis, reverse transcription polymerase ch ain reaction (PCR), RNA in situ hybridization, and immunohistochemistr y, All four medulloblastomas and five of the six medulloblastoma cell lines expressed transthyretin-mRNA as demonstrated by reverse PCR and in situ hybridization while three medulloblastomas and one cell line w ere positive on Northern blot. The medulloblastoma with the most abund ant RNA expression was transthyretin-immunoreactive on cryosections an d the medulloblastoma cell line that was positive on Northern blot als o expressed transthyretin at levels detectable by Western blot. No tra nsthyretin-immunoreactivity was seen in 16 additional medulloblastomas studied on paraffin sections. These findings indicate that low-level expression of transthyretin-mRNA is common in medulloblastomas and med ulloblastoma cell lines, Expression of transthyretin protein occurs ra rely but can reach significant levels. Transthyretin expression in med ulloblastoma is consistent with retinal pigment epithelium differentia tion in medulloblastomas and reflects their pluripotential nature, Fur thermore, the potential for transthyretin-immunoreactivity in medullob lastoma should be kept in mind when performing immunohistochemical stu dies on poorly differentiated cerebellar tumours.