Arville Brent, O'Rourke Emily, Chung Fai, Amin Mahul, Bose Shikha
Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Cytojournal. 2013 Dec 27;10:25. doi: 10.4103/1742-6413.123784. eCollection 2013.
Atypical urine cytology results trigger cystoscopy or molecular tests, both of which are costly, complex and difficult to perform tests. Several immunostains are being investigated to improve cancer detection; however, cytology material is limited and restricts the use of multiple immunostains. This study was designed to determine the utility of a cocktail of three stains, cytokeratin (CK20), p53 and CD44 in urine cytology samples for improving the detection of urothelial carcinoma.
Urine cytology specimens with cell blocks containing adequate cytologic material between 2005 and 2010 and subsequent follow-up biopsy and/or Urovysion test (102 cases including 29 negative, 56 atypical and 17 malignant) were included in the study and evaluated with the triple stain. Results were first validated on the positive and negative cases and then applied to the atypical cases to determine the utility in the diagnosis of urothelial carcinoma.
Based on the validation and published literature, two distinct immunoprofiles were defined - malignant, characterized by at least five CK20 and/or p53 positive atypical cells and reactive, all other staining patterns. The malignant immunoprofile showed 88% sensitivity, 78% specificity, 74% positive predictive value (PPV) and 90% negative predictive value (NPV) for detecting urothelial carcinoma. These values improved to 95% sensitivity and 96% NPV when low-grade urothelial carcinoma cases were excluded.
Our results indicate that the triple stain is an inexpensive, easy to perform test most useful for differentiating high-grade urothelial carcinoma from its mimics. However Inclusion of CD44 in the cocktail did not provide additional value and is best excluded.
非典型尿细胞学结果会引发膀胱镜检查或分子检测，这两种检测成本高、操作复杂且难度大。目前正在研究几种免疫染色方法以提高癌症检测率；然而，细胞学材料有限，限制了多种免疫染色的使用。本研究旨在确定细胞角蛋白（CK20）、p53和CD44三种染色剂的组合在尿细胞学样本中对提高尿路上皮癌检测的效用。
纳入2005年至2010年间含有足够细胞学材料的尿细胞学标本制作的细胞块，以及随后的随访活检和/或Urovysion检测（102例，包括29例阴性、56例非典型和17例恶性），并用三联染色进行评估。结果首先在阳性和阴性病例上进行验证，然后应用于非典型病例以确定其在尿路上皮癌诊断中的效用。
基于验证和已发表的文献，定义了两种不同的免疫表型——恶性，其特征为至少五个CK20和/或p53阳性非典型细胞；反应性，为所有其他染色模式。恶性免疫表型在检测尿路上皮癌时显示出88%的敏感性、78%的特异性、74%的阳性预测值（PPV）和90%的阴性预测值（NPV）。当排除低级别尿路上皮癌病例时，这些值提高到95%的敏感性和96%的NPV。
我们的结果表明，三联染色是一种廉价、易于操作的检测方法，最有助于将高级别尿路上皮癌与其模仿物区分开来。然而，在染色剂组合中加入CD44并未提供额外价值，最好将其排除。
