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Differential expression of SOX17 and SOX2 in germ cells and stem cells has biological and clinical implications

Authors

  • J de Jong,

    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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  • H Stoop,

    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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  • AJM Gillis,

    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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  • RJHLM van Gurp,

    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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  • G-JM van de Geijn,

    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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  • M de Boer,

    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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  • R Hersmus,

    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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  • PTK Saunders,

    1. Centre for Reproductive Biology, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK
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  • RA Anderson,

    1. Centre for Reproductive Biology, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, UK
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  • JW Oosterhuis,

    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
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  • LHJ Looijenga

    Corresponding author
    1. Department of Pathology, Erasmus MC–University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
    • Department of Pathology, Erasmus MC–University Medical Center Rotterdam (Daniel den Hoed Cancer Center), Josephine Nefkens Institute, Building Be, Room 430b, PO Box 2040, 3000 CA Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
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  • No conflicts of interest were declared.

Abstract

Combined action of SOX and POU families of transcription factors plays major roles in embryonic development. In embryonic stem cells, the combination of SOX2 and POU5F1 (OCT3/4) is essential for maintaining the undifferentiated state by activating pluripotency-linked genes, and inhibition of genes involved in differentiation. Besides embryonic stem cells, POU5F1 is also present in early germ cells, primordial germ cells, and gonocytes, where it has a role in suppression of apoptosis. Here we demonstrate that SOX2 is absent in germ cells of human fetal gonads, and as expected carcinoma in situ (CIS), ie the precursor lesion of testicular germ cell tumours of adolescents and adults (TGCTs), and seminoma. Based on genome-wide expression profiling, SOX17 was found to be present, instead of SOX2, in early germ cells and their malignant counterparts, CIS and seminoma. Immunohistochemistry, western blot analysis, and quantitative RT-PCR showed that SOX17 is a suitable marker to distinguish seminoma from embryonal carcinoma, confirmed in representative cell lines. Aberrant SOX2 expression can be present in Sertoli cells when associated with CIS, which can be misdiagnosed as embryonal carcinoma. In conclusion, this study demonstrates the absence of SOX2 in human embryonic and malignant germ cells, which express SOX17 in conjunction with POU5F1. This finding has both diagnostic and developmental biological implications. It allows the identification of seminoma-like cells from embryonal carcinoma based on a positive marker and might be the explanation for the different function of POU5F1 in normal and malignant germ cells versus embryonic stem cells. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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