New evidence for the origin of intracranial germ cell tumours from primordial germ cells: expression of pluripotency and cell differentiation markers.
Primary intracranial germ cell tumours are rare neoplasms that occur in children and adolescents. This study examined both the biology and the origin of these tumours, as it has been hypothesized that they originate from a totipotent primordial germ cell. We applied recent knowledge from gonadal germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected with their gonadal equivalents, including a close similarity with primordial germ cells. A notable difference was the sex-specific expression of TSPY, a gene previously implicated in the origin of gonadoblastoma. TSPY was only detected in germ cell tumours in the central nervous system (CNS) from males, suggesting that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which is a hallmark of primordial germ cells.
Hoei-Hansen
C E
CE
University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. chh@dadlnet.dk
Sehested
A
A
Juhler
M
M
Lau
Y-F C
YF
Skakkebaek
N E
NE
Laursen
H
H
Rajpert-de Meyts
E
E
D000293:Adolescent; D000328:Adult; D000943:Antigens, Differentiation / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D054278:Embryonal Carcinoma Stem Cells; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009373:Neoplasms, Germ Cell and Embryonal / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000943:Antigens, Differentiation; D009363:Neoplasm Proteins; D014157:Transcription Factors