Cytokeratin 20 immunocytochemistry on urine sediments: A potential low-cost adjunct to cytology in the diagnosis of low-grade urothelial carcinoma

Abstract

Background: 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.

Objective: 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.

Results: 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.

Conclusions: 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.

Keywords: cytokeratin 20; cytology; urine; urothelial carcinoma.