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Expression pattern of clinically relevant markers in paediatric germ cell- and sex-cord stromal tumours is similar to adult testicular tumours

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Abstract

Paediatric germ cell tumours (GCTs) are rare and account for less than 3 % of childhood cancers. Like adult GCTs, they probably originate from primordial germ cells, but the pattern of histopathological types is different, and they occur predominantly in extragonadal sites along the body midline. Because they are rare, histology of paediatric GCTs is poorly documented, and it remains unclear to what extent they differ from adult GCTs. We have analysed 35 paediatric germ cell tumours and 5 gonadal sex-cord stromal tumours from prepubertal patients aged 0–15 years, to gain further knowledge, elaborate on clinical-pathological associations and better understand their developmental divergence. The tumours were screened for expression of stemness-related factors (OCT4, AP-2γ, SOX2), classical yolk sac tumours (YSTs; AFP, SALL4), GCTs (HCG, PLAP, PDPN/D2-40), as well as markers for sex-cord stromal tumour (PDPN, GATA4). All YSTs expressed AFP and SALL4, with GATA4 present in 13/14. The majority of teratomas expressed SOX2 and PDPN, whereas SALL4 was found in 8/13 immature teratomas. Adult seminoma markers AP-2γ, OCT4, SALL4 and PDPN were all expressed in dysgerminoma. We further report a previously unrecognised pathogenetic relationship between AFP and SALL4 in YST in that different populations of YST cells express either SALL4 or AFP, which suggests variable differentiation status. We also show that AP-2γ is expressed in the granulosa layer of ovarian follicles and weakly expressed in immature but not in mature granulosa cell tumours. Our findings indicate that the expression pattern of these antigens is similar between paediatric and adult GCTs, even though they develop along different developmental trajectories.

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Acknowledgements

We thank B. Håkansson and C. Campen for technical support and Dr Jesper Sune Brok for useful comments. We are grateful to Drs. R. Cate (Biogen) and G. Spagnoli (University of Basel) for providing antibodies against AMH and MAGE-A4, respectively. This work was supported by the Danish Cancer Society (No. R64-A3702-12-S7), the Danish Child Cancer Foundation (No. 2010-39 and 2013-16) and the Research Fund at Rigshospitalet (grant 9615.06.1.15).

Author contribution

CEHH, ERM and CR conceived and planned the study. BGT and BLP performed pathological revision. CHM, JEN and TS designed and performed the experiments. CHM, TS, JEN and CEHH evaluated IHC and IF. CHM and CEHH collected clinical data. All authors contributed to writing and revising the paper.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Christiane Hammershaimb Mosbech, Terje Svingen, John Erik Nielsen, Ewa Rajpert-De Meyts & Christina Engel Hoei-Hansen

  2. Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Birgitte Groenkaer Toft

  3. Department of Paediatrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Catherine Rechnitzer

  4. Department of Pathology, University Hospital Roskilde, Roskilde, Denmark

    Bodil Laub Petersen

  5. Department of Paediatrics, University Hospital Hillerød, Dyrehavevej 29, 3400, Hillerød, Denmark

    Christina Engel Hoei-Hansen

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  1. Christiane Hammershaimb Mosbech
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  2. Terje Svingen
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  3. John Erik Nielsen
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  8. Christina Engel Hoei-Hansen
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Correspondence to Christina Engel Hoei-Hansen.

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Mosbech, C.H., Svingen, T., Nielsen, J.E. et al. Expression pattern of clinically relevant markers in paediatric germ cell- and sex-cord stromal tumours is similar to adult testicular tumours. Virchows Arch 465, 567–577 (2014). https://doi.org/10.1007/s00428-014-1635-1

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