Department of Urology, University Hospital Basel, Basel, Switzerland.
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
Cancer Cytopathol. 2019 Sep;127(9):578-585. doi: 10.1002/cncy.22167. Epub 2019 Aug 6.
Mutations of AT-rich interactive domain 1 (ARID1A) have been associated with a worse outcome after intravesical treatment with bacille Calmette-Guérin in patients with non-muscle-invasive bladder cancer (NMIBC). Loss of ARID1A protein expression in urine cytology may serve as an indication of an ARID1A mutation. Therefore, the authors examined the expression of ARID1A in urine cytology and histological specimens of bladder cancer for correlation with ARID1A mutational status.
The authors constructed a tissue microarray containing samples from 164 tissue samples from 150 patients with NMIBC and 100 tissue samples from 81 patients with muscle-invasive bladder cancer. A second cohort consisted of archived cytological specimens and matched tissue sections from 62 patients with high-grade NMIBC. The authors established immunohistochemistry and immunocytochemistry (ICC) protocols, respectively, for the analysis of ARID1A protein expression in histological and cytological specimens. Confirmatory next-generation sequencing (NGS) was performed on tumor specimens using a targeted NGS panel containing all exonic regions of ARID1A.
The prevalence of ARID1A loss of expression on the tissue microarray was 3.6% in NMIBC (6 of 164 tissue samples) and 10% in muscle-invasive bladder cancer (10 of 100 tissue samples) (P = .059). Loss of ARID1A expression in cytology was concordantly immunohistochemistry negative in 6 of 8 matched tissue specimens. NGS confirmed an ARID1A mutation on all 6 histology samples with loss of ARID1A expression. When NGS demonstrated an absence of ARID1A mutation, histology was concordantly positive (16 of 16 cases).
The authors have suggest ARID1A ICC as a promising surrogate marker for ARID1A mutational status in patients with urothelial carcinoma. Pitfalls in ICC scoring include benign umbrella cells that often are negative for ARID1A. Further prospective studies are needed to determine the clinical relevance of ARID1A ICC in urinary cytology.
富含 AT 丰富相互作用域 1（ARID1A）的突变与非肌肉浸润性膀胱癌（NMIBC）患者经卡介苗膀胱内治疗后的预后较差相关。尿液细胞学中 ARID1A 蛋白表达的缺失可能是 ARID1A 突变的一个指标。因此，作者研究了膀胱癌尿液细胞学和组织学标本中 ARID1A 的表达，以与 ARID1A 突变状态相关。
作者构建了一个组织微阵列，包含来自 150 名 NMIBC 患者的 164 个组织样本和 81 名肌肉浸润性膀胱癌患者的 100 个组织样本。第二个队列由 62 名高级别 NMIBC 患者的存档细胞学标本和匹配的组织切片组成。作者分别建立了用于分析组织学和细胞学标本中 ARID1A 蛋白表达的免疫组化和免疫细胞化学（ICC）方案。使用包含 ARID1A 所有外显子区域的靶向 NGS 面板对肿瘤标本进行了确认性下一代测序（NGS）。
在组织微阵列中，NMIBC 的 ARID1A 表达缺失率为 3.6%（164 个组织样本中的 6 个），肌肉浸润性膀胱癌为 10%（100 个组织样本中的 10 个）（P=0.059）。在 8 个匹配的组织标本中，6 个标本的细胞学 ARID1A 表达缺失与免疫组化阴性一致。NGS 证实了所有 6 个组织学样本中 ARID1A 缺失，且均存在 ARID1A 突变。当 NGS 显示不存在 ARID1A 突变时，组织学结果与之一致（16 例均为阳性）。
作者提出了 ARID1A ICC 作为一种有前途的尿路上皮癌患者 ARID1A 突变状态的替代标志物。ICC 评分中的陷阱包括经常为 ARID1A 阴性的良性伞细胞。需要进一步的前瞻性研究来确定尿液细胞学中 ARID1A ICC 的临床相关性。
