Identification of novel diagnostic markers for choroid plexus tumors: a microarray-based approach.
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.
Hasselblatt
Martin
M
Institute of Neuropathology, University Hospital Münster, Domagkstrasse 19, 48129 Münster, Germany. hasselblatt@uni-muenster.de
Böhm
Christine
C
Tatenhorst
Lars
L
Dinh
Vinzenz
V
Newrzella
Dieter
D
Keyvani
Kathy
K
Jeibmann
Astrid
A
Buerger
Horst
H
Rickert
Christian H
CH
Paulus
Werner
W
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016545:Choroid Plexus Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D003937:Diagnosis, Differential; D004805:Ependyma / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D020288:Papilloma, Choroid Plexus / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D006023:Glycoproteins; C489477:Kir7.1 channel; D024661:Potassium Channels, Inwardly Rectifying; C051795:teleocalcin