Wadhwa N, Diwaker P, Lotha N, Arora V K, Singh N
Department of Pathology, University College of Medical Sciences, University of Delhi, Shahdra, Delhi, India.
Cytopathology. 2017 Dec;28(6):531-535. doi: 10.1111/cyt.12463. Epub 2017 Sep 22.
Urine cytology is the corner-stone for the diagnosis of urothelial neoplasia; however, a substantial proportion of low-grade carcinomas are reported as inconclusive owing to scant cellularity and subtle cytological features. Biomarkers applied on urine sediment smears of such patients are likely to be clinically relevant. Access to Food and Drug Administration approved urinary biomarkers in resource limited setting is poor. Detection of cytokeratin 20 (CK20) in urine sediments, although still a research tool, is a promising marker as immunocytochemistry is performed regularly in several Indian laboratories.
We tested the clinical utility of CK20 immunocytochemistry as a potential low-cost adjunct to urine cytology in diagnosis of low-grade urothelial carcinoma. One hundred and fifty fresh, voided urine specimens from 42 cases of biopsy proven urothelial neoplasia (14 high grade, 28 combined low-grade [n=26]) and low malignant potential [n=2]), and 20 non-neoplastic lesions were included in the study sample.
Confident diagnosis of malignancy was possible in five (17.8%) low-grade malignancies. Thirteen of 16 (81.3%) low-grade malignancies with inconclusive cytology showed positive CK20 expression. This reduced the proportion of low-grade cases with inconclusive cytology from 57.1% to 10.7% (P=.021). In addition, we could correctly classify one case of bladder lithiasis with false positive urine cytology. Discrepant CK20 staining (positive) was seen in one patient with acute cystitis.
CK20 expression in non-umbrella cells is a robust marker of urinary bladder carcinoma. It has potential clinical utility for identification of low-grade urothelial malignancy with inconclusive cytological diagnosis.
尿细胞学检查是诊断尿路上皮肿瘤的基石；然而，相当一部分低级别癌因细胞数量少和细胞学特征不明显而报告为诊断不明确。应用于这类患者尿沉渣涂片的生物标志物可能具有临床相关性。在资源有限的环境中，获得美国食品药品监督管理局批准的尿生物标志物的情况较差。尿沉渣中细胞角蛋白20（CK20）的检测虽然仍是一种研究工具，但作为一种有前景的标志物，免疫细胞化学在印度的几个实验室中经常进行。
我们测试了CK20免疫细胞化学作为尿细胞学检查的潜在低成本辅助手段在诊断低级别尿路上皮癌中的临床应用价值。研究样本包括来自42例经活检证实的尿路上皮肿瘤（14例高级别、28例低级别合并[26例]）和低恶性潜能[2例]患者的150份新鲜晨尿标本，以及20份非肿瘤性病变标本。
5例（17.8%）低级别恶性肿瘤得以明确诊断。16例细胞学诊断不明确的低级别恶性肿瘤中有13例（81.3%）CK20表达阳性。这将细胞学诊断不明确的低级别病例比例从57.1%降至10.7%（P=0.021）。此外，我们能够正确分类1例假阳性尿细胞学检查的膀胱结石病例。1例急性膀胱炎患者出现了不一致的CK20染色（阳性）。
非伞状细胞中CK20的表达是膀胱癌的一个可靠标志物。它在鉴别细胞学诊断不明确得低级别尿路上皮恶性肿瘤方面具有潜在的临床应用价值。
