Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
Virchows Arch. 2020 Nov;477(5):651-660. doi: 10.1007/s00428-020-02839-z. Epub 2020 May 23.
The presence of sarcomatoid or rhabdoid features (which are associated with advanced disease and poor prognosis) is rarely observed in the subtypes of renal cell carcinoma (RCC). The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits including SMARCB1/INI1 (SMARCB1), SMARCA4/BRG1 (SMARCA4), SMARCC1/BAF155 (SMARCC1), and SMARCC2/BAF170 (SMARCC2), can be regarded as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. We analyzed the histological, immunohistochemical, and clinicopathological status in 72 cases of RCC with sarcomatoid or rhabdoid features, focusing on the expression status of the subunits of SWI/SNF chromatin-remodeling complex proteins. Cases with lost or reduced expression were defined as showing aberrant expression. The frequency of aberrant SMARCA4 immunoexpression of a sarcomatoid or rhabdoid component in clear cell RCC (ccRCC) (47/50, 94%) was significantly higher than that in non-ccRCC (4/9, 44%) (p < 0.001). In ccRCC without sarcomatoid or rhabdoid features, aberrant SMARCA4 immunoexpression was observed in 33 of 48 (67%) cases. Immunoreactivities for SMARCB1, SMARCA2, and SMARCC2 were retained in almost all subtypes of RCC. The patients with aberrant SMARCA4 expression in RCC with sarcomatoid or rhabdoid features achieved shorter progression-free survival compared with the patients with retained SMARCA4 expression (all subtypes of RCC, p = 0.0212; ccRCC, p = 0.0265). These results suggest that in ccRCC, aberrant SMARCA4 expression is one of the adverse prognostic factors or a high-grade malignant transforming factor. The evaluation of SMARCA4 immunoexpression may be a useful diagnostic tool to help distinguish ccRCC from non-ccRCC.
肉瘤样或横纹肌样特征（与晚期疾病和预后不良相关）在肾细胞癌（RCC）的亚型中很少观察到。SWI/SNF 染色质重塑复合物由进化上保守的核心亚基组成，包括 SMARCB1/INI1（SMARCB1）、SMARCA4/BRG1（SMARCA4）、SMARCC1/BAF155（SMARCC1）和 SMARCC2/BAF170（SMARCC2），可以被视为涉及肿瘤抑制的基因表达表观遗传调节剂的原型。我们分析了 72 例具有肉瘤样或横纹肌样特征的 RCC 的组织学、免疫组织化学和临床病理状态，重点研究了 SWI/SNF 染色质重塑复合物蛋白亚基的表达状态。将缺失或表达减少的病例定义为显示异常表达。在透明细胞肾细胞癌（ccRCC）（47/50，94%）中具有肉瘤样或横纹肌样成分的异常 SMARCA4 免疫表达的频率明显高于非 ccRCC（4/9，44%）（p<0.001）。在没有肉瘤样或横纹肌样特征的 ccRCC 中，33 例（67%）病例中观察到异常 SMARCA4 免疫表达。SMARCB1、SMARCA2 和 SMARCC2 的免疫反应性几乎保留在 RCC 的所有亚型中。在具有肉瘤样或横纹肌样特征的 RCC 中具有异常 SMARCA4 表达的患者与具有保留 SMARCA4 表达的患者相比，无进展生存期更短（所有 RCC 亚型，p=0.0212；ccRCC，p=0.0265）。这些结果表明，在 ccRCC 中，异常 SMARCA4 表达是不良预后因素之一或高级别恶性转化因素。SMARCA4 免疫表达的评估可能是一种有用的诊断工具，有助于区分 ccRCC 和非 ccRCC。
