title: Thyroid transcription factor-1 distinguishes subependymal giant cell astrocytoma from its mimics and supports its cell origin from the progenitor cells in the medial ganglionic eminence.
abstract: Subependymal giant cell astrocytoma is a benign brain tumor mostly associated with tuberous sclerosis complex. However, it may be misinterpreted as other high-grade brain tumors due to the presence of large tumor cells with conspicuous pleomorphism and occasional atypical features, such as tumor necrosis and endothelial proliferation. In this study, we first investigated thyroid transcription factor-1 (TTF-1) expression in a large series of subependymal giant cell astrocytomas and other histologic and locational mimics to validate the diagnostic utility of this marker. We then examined TTF-1 expression in non-neoplastic brain tissue to determine the cell origin of subependymal giant cell astrocytoma. Twenty-four subependymal giant cell astrocytoma specimens were subjected to tissue microarray construction. For comparison, a selection of tumors, including histologic mimics (21 gemistocytic astrocytomas and 24 gangliogliomas), tumors predominantly occurring at the ventricular system (50 ependymomas, 19 neurocytomas, and 7 subependymomas), and 134 astrocytomas (3 pleomorphic xanthoastrocytomas, 45 diffuse astrocytomas, 46 anaplastic astrocytomas, and 40 glioblastomas) were used. Immunohistochemical stain for TTF-1 was positive in all 24 subependymal giant cell astrocytomas, whereas negative in all astrocytomas, gangliogliomas, ependymomas, and subependymomas. Neurocytomas were positive for TTF-1 in 4/19 (21%) of cases using clone 8G7G3/1 and in 9/19 (47%) of cases using clone SPT24. In the three fetal brains that we examined, TTF-1 expression was seen in the medial ganglionic eminence, a transient fetal structure between the caudate nucleus and the thalami. There was no BRAFV600Emutation identified by direct sequencing in the 20 subependymal giant cell astrocytomas that we studied. In conclusion, TTF-1 is a useful marker in distinguishing subependymal giant cell astrocytoma from its mimics. Expression of TTF-1 in the fetal medial ganglionic eminence indicates that subependymal giant cell astrocytoma may originate from the progenitor cells in this region.
authors.affiliation: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jen-Fan
authors.initials: JF
authors.lastname: Hang
authors.affiliation: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chih-Chun
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Han-Jui
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Donald Ming-Tak
authors.initials: DM
authors.lastname: Ho
mesh_terms: D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D018303:Ganglioglioma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D005909:Glioblastoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000074482:Thyroid Nuclear Factor 1