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

• Published in: Virchows Archiv : an international journal of pathology Vol. 470; no. 4; pp. 421 - 428
• Main Authors: Bremmer, F., Behnes, C. L., Schildhaus, H. U., Gaisa, N. T., Reis, H., Jarry, H., Radzun, H. J., Stroebel, P., Schweyer, S.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2017; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; beta Catenin - analysis; beta Catenin - biosynthesis; Biomarkers, Tumor - analysis; DNA Mutational Analysis; Humans; Immunohistochemistry; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Original Article; Pathology; Sex Cord-Gonadal Stromal Tumors - diagnosis; Sex Cord-Gonadal Stromal Tumors - genetics; Sex Cord-Gonadal Stromal Tumors - metabolism; SOX9 Transcription Factor - analysis; SOX9 Transcription Factor - biosynthesis; Testicular Neoplasms - diagnosis; Testicular Neoplasms - genetics; Testicular Neoplasms - metabolism; Tumors; Immunohistochemistry; Sertoli cell tumours; SOX9; Cyclin D1; Leydig cell tumours; Beta-catenin
• DOI: 10.1007/s00428-017-2090-6
• ISSN: 0945-6317

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.