Bremmer F, Behnes C L, Schildhaus H U, Gaisa N T, Reis H, Jarry H, Radzun H J, Stroebel P, Schweyer S
Institute of Pathology, University Medical Center Göttingen, Robert-Koch-Str.40, 37075, Göttingen, Germany.
Institute of Pathology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Virchows Arch. 2017 Apr;470(4):421-428. doi: 10.1007/s00428-017-2090-6. Epub 2017 Feb 16.
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.
世界卫生组织（WHO）对睾丸肿瘤的分类包括性索间质肿瘤组。它们被分为几种组织学类型，即莱迪希细胞瘤（LCT）和支持细胞瘤（SCT）。基于β-连环蛋白在正常睾丸/支持细胞中的生理表达，先前的研究表明，SCT可能携带β-连环蛋白突变，导致β-连环蛋白和细胞周期蛋白D1的核阳性。此外，研究还发现，支持细胞中β-连环蛋白的稳定会导致支持细胞标志物SOX9的丢失。我们想了解性索间质肿瘤中β-连环蛋白的稳定是否会影响SOX-9的表达，从而可用于性索间质肿瘤的诊断。因此，我们对53例性索间质肿瘤和肿瘤样病变进行了β-连环蛋白、细胞周期蛋白D1和SOX9的免疫组化表达研究。此外，还对β-连环蛋白基因（外显子3；CTNNB1）进行了突变分析。免疫组化分析显示，SCT中的β-连环蛋白突变导致核β-连环蛋白和细胞周期蛋白D1表达。β-连环蛋白的核表达/稳定导致这些肿瘤中SOX9的丢失。相比之下，SOX9在未发生突变的SCT以及非肿瘤性睾丸的支持细胞中大量表达。总之，β-连环蛋白和SOX9的免疫组化分析有助于区分SCT与睾丸的其他性索间质肿瘤。此外，SOX9的存在表明细胞起源可能是支持细胞。
