背景:睾丸间质细胞肿瘤(LCT)是男性最常见的性索间质肿瘤,占所有睾丸肿瘤的1%-3%。在睾丸性索间质肿瘤中,CTNNB1突变和β-连环蛋白的核表达通常与支持细胞肿瘤有关。最近的基因组分析表明,CTNNB1变体也在LCT的一个子集中被鉴定出来;然而,在这种肿瘤类型中,β-catenin改变的频率和临床病理相关性仍未完全了解.
方法:在本研究中,我们评估了32个LCTs(5个恶性/转移,27非转移)使用β-连环蛋白免疫组织化学和DNA测序。
结果:免疫组织化学显示47%的肿瘤中有局灶性或多灶性核β-catenin表达。在本文分析的任何病例中均未检测到弥漫性核β-连环蛋白表达(在>50%的肿瘤细胞中)。β-catenin阳性和β-catenin阴性病例的比较在不良组织病理学发现或恶性临床行为的频率上没有显着差异。从头对7例病例的一个子集进行的DNA测序显示,其中4例(4/7,57%)存在外显子3CTNNB1变体,变异等位基因频率(VAF)范围为7%至33%。作为先前研究的一部分进行测序的另外两个β-catenin阳性病例在VAF为28%和7%时含有外显子3CTNNB1变体,分别。
结论:这些结果表明β-连环蛋白改变在LCT中相对常见,最有可能发生在具有侵袭性特征的病例中没有富集的亚克隆事件。需要进一步的研究来阐明β-连环蛋白在这种肿瘤类型中的致癌作用。
BACKGROUND: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord-stromal tumour in men, representing 1%-3% of all testicular neoplasms. Among testicular sex cord-stromal tumours, CTNNB1 mutations and nuclear expression of β-catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of β-catenin alterations remain incompletely understood in this tumour type.
METHODS: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using β-catenin immunohistochemistry and DNA sequencing.
RESULTS: Immunohistochemistry revealed focal or multifocal nuclear β-catenin expression in 47% of the tumours. Diffuse nuclear β-catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of β-catenin-positive and β-catenin-negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional β-catenin-positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively.
CONCLUSIONS: These results demonstrate that β-catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of β-catenin in this tumour type.