Abstract
Central nervous system (CNS) germ cell tumors constitute a unique class of rare tumors that mainly affect children and adolescents. These tumors are believed to originate from displaced primordial germ cells. Recently, results of treatment of germ cell tumors have improved with use of radiotherapy and combination chemotherapy. However, some tumors have proven refractory to intensive treatment with surgery, radiation, and combination chemotherapy. Nestin is an intermediate filament protein expressed in undifferentiated cells during CNS development and in CNS tumors and is used as a marker of immature elements of tumors, including brain tumor stem cells. In this study, we examined for the first time nestin expression in 19 CNS germ cell tumors (nine pure germinomas, five germinomas with syncytiotrophoblastic giant cells, one yolk sac tumor, one choriocarcinoma, one embryonal carcinoma, and two mature teratomas). Nestin was expressed in 14 cases but was not expressed in three pure germinomas and two mature teratomas. Clinically, nestin-negative tumors did not exhibit dissemination, while all tumors that exhibited dissemination also strongly expressed nestin protein. These findings suggest that the detection of nestin expression could be useful in the management of CNS germ cell tumors, as an auxiliary predictor of dissemination and/or progression.
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Matthias Kirsch, Gabriele Schackert, Dresden, Germany
In the present paper, Sakurada et al. demonstrated the preferential appearance of Nestin-positive tumor cells in disseminated versus local germ cell tumors. This finding might be relevant for therapeutic decisions upon early, although radiologically unproven dissemination.
In addition, the authors relate to the possibility of a potential germinoma stem-like cell population. For this purpose, CD133 or prominin-1 is most prominently used as a tumor stem cell marker although neither function nor pathogenetic role is known. Recently, CD133+ glioma–initiating cells are tumorigenic in vivo even after serial transplantation (reviewed in [1, 3]. These brain tumor stem cells represent 1% to 30% of the total cell number and show characteristics of neural stem cells. Their unique potential for chemotherapy and radiation therapy resistance has enormous implications on our current understanding of tumor biology and treatment rationals. Regarding germ cell tumors, up-to-date, only one additional embryonic stem cell factor has been associated with another type of germ cell tumors: sox2 is expressed in embryonal carcinoma but not pure seminoma [2]. Therefore, an exciting road of future investigations lies ahead: characterization of CD133 and other stemness markers in germinomas, isolation and propagation of tumor-initiating cells, as well as a demonstration of their tumorigenicity in vivo.
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3. Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nature Reviews Cancer 6(June):425
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Sakurada, K., Saino, M., Mouri, W. et al. Nestin expression in central nervous system germ cell tumors. Neurosurg Rev 31, 173–177 (2008). https://doi.org/10.1007/s10143-007-0115-3
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DOI: https://doi.org/10.1007/s10143-007-0115-3