Skip to main content

Advertisement

SpringerLink
Log in

The role of beta-catenin mutation and SOX9 expression in sex cord-stromal tumours of the testis

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The WHO classification of testis tumours includes the group of sex cord-stromal tumours. They are divided into several histological types, i.e. Leydig cell (LCT) and Sertoli cell tumours (SCT). Based on the physiological expression of β-catenin in normal testis/Sertoli cells, it was previously shown that SCT can carry a β-catenin mutation, causing a nuclear positivity for β-catenin and cyclin D1. Furthermore, it could be shown that the stabilization of β-catenin in Sertoli cells causes the loss of the Sertoli cell marker SOX9. We wanted to know whether the stabilization of β-catenin in sex cord-stromal tumours influences SOX-9 expression and thus could be used in the diagnosis of sex cord-stromal tumours. Therefore, 53 cases of sex cord-stromal tumours and tumour-like lesions were investigated for their immunohistochemical expressions of β-catenin, cyclin D1 and SOX9. In addition, mutation analyses of the β-catenin gene (exon 3; CTNNB1) were performed. β-catenin mutation in SCT results in nuclear β-catenin and cyclin-D1 expressions on immunohistochemical analysis. The nuclear expression/stabilization of β-catenin causes the loss of SOX9 in these tumours. In contrast, SOX9 is considerably expressed in non-mutated SCT as well as in Sertoli cells of non-neoplastic testes. In summary, immunohistochemical analyses of β-catenin and SOX9 are useful to distinguish SCT from other sex cord-stromal tumours of the testis. Furthermore, the presence of SOX9 indicates that the cells of origin may be Sertoli cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Oliva E, Young RH, Ulbright TM (2016) Sex cord-stromal tumours. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE (eds) WHO classification of tumours of the urinary system and male genital organs. IARC, Lyon

    Google Scholar 

  2. Xiao GQ, Granato RC, Unger PD (2012) Bilateral Sertoli cell tumors of the testis—a likely new extracolonic manifestation of familial adenomatous polyposis. Virchows Archiv : an international journal of pathology. 461(6):713–715. doi:10.1007/s00428-012-1332-x

    Article  CAS  Google Scholar 

  3. Galiatsatos P, Foulkes WD (2006) Familial adenomatous polyposis. Am J Gastroenterol 101(2):385–398. doi:10.1111/j.1572-0241.2006.00375.x

    Article  PubMed  Google Scholar 

  4. Aoki K, Taketo MM (2007) Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci 120(Pt 19):3327–3335. doi:10.1242/jcs.03485

    Article  CAS  PubMed  Google Scholar 

  5. Lips DJ, Barker N, Clevers H, Hennipman A (2009) The role of APC and beta-catenin in the aetiology of aggressive fibromatosis (desmoid tumors). European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 35(1):3–10. doi:10.1016/j.ejso.2008.07.003

    Article  CAS  Google Scholar 

  6. Nollet F, Berx G, van Roy F (1999) The role of the E-cadherin/catenin adhesion complex in the development and progression of cancer. Molecular cell biology research communications: MCBRC 2(2):77–85. doi:10.1006/mcbr.1999.0155

    Article  CAS  PubMed  Google Scholar 

  7. Perrone F, Bertolotti A, Montemurro G, Paolini B, Pierotti MA, Colecchia M (2014) Frequent mutation and nuclear localization of beta-catenin in Sertoli cell tumors of the testis. Am J Surg Pathol 38(1):66–71. doi:10.1097/PAS.0b013e31829cdbc6

    Article  PubMed  Google Scholar 

  8. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B et al (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275(5307):1787–1790

    Article  CAS  PubMed  Google Scholar 

  9. Chaboissier MC, Kobayashi A, Vidal VI, Lutzkendorf S, van de Kant HJ, Wegner M et al (2004) Functional analysis of Sox8 and Sox9 during sex determination in the mouse. Development 131(9):1891–1901. doi:10.1242/dev.01087

    Article  CAS  PubMed  Google Scholar 

  10. Chang H, Gao F, Guillou F, Taketo MM, Huff V, Behringer RR (2008) Wt1 negatively regulates beta-catenin signaling during testis development. Development 135(10):1875–1885. doi:10.1242/dev.018572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bremmer F, Strobel P, Jarry H, Strecker J, Gaisa N, Strauss A et al (2015) CK19 is a sensitive marker for yolk sac tumours of the testis. Diagn Pathol 10:7. doi:10.1186/s13000-015-0243-y

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zhang C, Ulbright TM (2015) Nuclear localization of beta-catenin in Sertoli cell tumors and other sex cord-stromal tumors of the testis: an immunohistochemical study of 87 cases. Am J Surg Pathol 39(10):1390–1394. doi:10.1097/PAS.0000000000000455

    Article  PubMed  Google Scholar 

  13. Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC et al (2006) Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol 4(6):e187. doi:10.1371/journal.pbio.0040187

    Article  PubMed  PubMed Central  Google Scholar 

  14. De Santa BP, Bonneaud N, Boizet B, Desclozeaux M, Moniot B, Sudbeck P et al (1998) Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Mullerian hormone gene. Mol Cell Biol 18(11):6653–6665

    Article  Google Scholar 

  15. Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S et al (2009) The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development 136(11):1813–1821. doi:10.1242/dev.032631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bouma GJ, Albrecht KH, Washburn LL, Recknagel AK, Churchill GA, Eicher EM (2005) Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells. Development 132(13):3045–3054. doi:10.1242/dev.01890

    Article  CAS  PubMed  Google Scholar 

  17. Papanastasopoulos P, Repanti M, Damaskou V, Bravou V, Papadaki H (2008) Investigating differentiation mechanisms of the constituent cells of sex cord-stromal tumours of the ovary. Virchows Archiv : an international journal of pathology 453(5):465–471. doi:10.1007/s00428-008-0677-7

    Article  CAS  Google Scholar 

  18. Kao CS, Cornejo KM, Ulbright TM, Young RH (2015) Juvenile granulosa cell tumors of the testis: a clinicopathologic study of 70 cases with emphasis on its wide morphologic spectrum. Am J Surg Pathol 39(9):1159–1169. doi:10.1097/PAS.0000000000000450

    Article  PubMed  Google Scholar 

  19. Al-Fageeh M, Li Q, Dashwood WM, Myzak MC, Dashwood RH (2004) Phosphorylation and ubiquitination of oncogenic mutants of beta-catenin containing substitutions at Asp32. Oncogene 23(28):4839–4846. doi:10.1038/sj.onc.1207634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Valerie Unterkircher and Stefan Kueffer for the perfect technical assistance. Felix Bremmer is supported by the research program of the Faculty of Medicine, Georg-August-University Göttingen and the Wilhelm-Sander-Stiftung (2016.041.1).

Author information

Authors and Affiliations

  1. Institute of Pathology, University Medical Center Göttingen, Robert-Koch-Str.40, 37075, Göttingen, Germany

    F. Bremmer, C. L. Behnes, H. U. Schildhaus, H. J. Radzun & P. Stroebel

  2. Institute of Pathology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany

    N. T. Gaisa

  3. Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany

    H. Reis

  4. Experimental Endocrinology, University Medical Center Göttingen, Robert-Koch-Str.40, 37075, Göttingen, Germany

    H. Jarry

  5. Gemeinschaftspraxis Pathologie, Am Fuchsengraben 3, 82319, Starnberg, Germany

    S. Schweyer

Authors
  1. F. Bremmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. L. Behnes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. U. Schildhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. T. Gaisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. Jarry
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. J. Radzun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P. Stroebel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. Schweyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Bremmer.

Ethics declarations

Ethical approval

Ethical approval for using human material in the present study was obtained from the ethics committee of the University Medical Centre Göttingen (application number: 2/6/16).

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bremmer, F., Behnes, C.L., Schildhaus, H.U. et al. The role of beta-catenin mutation and SOX9 expression in sex cord-stromal tumours of the testis. Virchows Arch 470, 421–428 (2017). https://doi.org/10.1007/s00428-017-2090-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-017-2090-6

Keywords

Search

Navigation