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

Virchows Arch. 2017 Apr;470(4):421-428. doi: 10.1007/s00428-017-2090-6. Epub 2017 Feb 16.

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.

Keywords: Beta-catenin; Cyclin D1; Immunohistochemistry; Leydig cell tumours; SOX9; Sertoli cell tumours.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • DNA Mutational Analysis
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation
  • SOX9 Transcription Factor / analysis
  • SOX9 Transcription Factor / biosynthesis*
  • Sex Cord-Gonadal Stromal Tumors / diagnosis*
  • Sex Cord-Gonadal Stromal Tumors / genetics
  • Sex Cord-Gonadal Stromal Tumors / metabolism
  • Testicular Neoplasms / diagnosis*
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / metabolism
  • beta Catenin / analysis
  • beta Catenin / biosynthesis*

Substances

  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • beta Catenin