RESUMO
To identify specific markers for the diagnosis of choroid plexus tumors, gene expression profiles of choroid plexus epithelial cells (n = 8) and ependymal cells (n = 6) microdissected from human autopsy brains as well as choroid plexus papilloma tissue were investigated using DNA microarrays. Protein expression of genes overexpressed in choroid plexus was evaluated in normal choroid plexus, choroid plexus papilloma, choroid plexus carcinoma, other primary brain tumors, and cerebral metastases. Forty-six genes found to be overexpressed in normal choroid plexus epithelial cells were also present in choroid plexus papilloma. Among those, 11 were further analyzed by immunohistochemistry. Expression of inward rectifier potassium channel Kir7.1 was confirmed in normal choroid plexus (34 of 35), choroid plexus papilloma (12 of 18), and choroid plexus carcinoma (5 of 5) but was not found in 100 other primary brain tumors and cerebral metastases. Similarly, stanniocalcin-1 stained normal choroid plexus (32 of 35), choroid plexus papilloma (16 of 18), and choroid plexus carcinoma (3 of 5), whereas staining was seen in only 2 of 100 other primary brain tumors and cerebral metastases. Transthyretin stained choroid plexus (33 of 35), choroid plexus papilloma (14 of 18), and plexus carcinoma (2 of 5), but its specificity was significantly lower. Antibodies directed against coagulation factor V, glutathione peroxidase 3, pigment epithelium derived factor, serotonin receptor 5-HTR2C, lumican, fibulin-1, plastin-1, and cytokeratin 18 revealed varying degrees of specificity and sensitivity. Our data suggest that antibodies directed against Kir7.1 and stanniocalcin-1 might serve as sensitive and specific diagnostic markers for choroid plexus tumors.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Plexo Corióideo/diagnóstico , Papiloma do Plexo Corióideo/diagnóstico , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias do Plexo Corióideo/genética , Neoplasias do Plexo Corióideo/metabolismo , Diagnóstico Diferencial , Epêndima/metabolismo , Epêndima/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Glicoproteínas/metabolismo , Humanos , Imuno-Histoquímica , Análise de Sequência com Séries de Oligonucleotídeos , Papiloma do Plexo Corióideo/genética , Papiloma do Plexo Corióideo/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeRESUMO
The complexity of the brain makes the investigation of anatomically defined regions using manual dissection techniques problematic. With these manual dissection techniques, only a mixture of many different cell types can be obtained. This leads to averaging the contents of all the different cell types, making it nearly impossible to observe effects that are specific to one type of cell. Laser microdissection enables individual cell-types to be dissected accurately from the brain for subsequent analysis of the genome, proteome or, most frequently, the transcriptome. Investigating only functionally relevant cells with high specificity provides unambiguous data, resulting in faster identification of potential targets, the elucidation of drug mode-of-action, as well as aiding identification of biomarkers for diagnostics use.