Diagnostic Significance of Cytokeratin 20 and p53 as Adjunct Immunocytological Markers in Urine Cytology to Detect Urothelial Carcinomas: A Systematic Review Study

The progression and recurrence of urothelial carcinoma (UC) are correlated with carcinoma in situ and urothelial dysplasia. It is frequently challenging to distinguish dysplasia and carcinoma in situ from reactive atypia only based on histological characteristics. In daily practices, 2 of the adjunct immunohistochemistry markers (cytokeratin 20 (CK20) and p53) are used in addition to the histology to diagnose carcinoma in situ. This is accomplished by combining histological research results with immunohistochemistry. This systematic review summarizes the current findings on the diagnostic significance of p53 and CK20 as adjunct markers to urine cytology in the detection of UC. A systematic search of the relevant literature was conducted using PubMed, Wiley Online Library, and ScienceDirect databases. After screening for the eligibility criteria, a total of 14 selected articles were reviewed. Data extraction included a total number of samples, specimen samples, type of cells, and outcome parameters (mainly sensitivity and specificity). Urine cytology alone had a sensitivity of 75%-85% and specificity of 66%-95%. CK20 with urine cytology staining showed improved sensitivity and specificity in the range of 77%-94% and 71%-100%, respectively; p53 immunostaining with urine cytology showed a sensitivity of 52%-86% and specificity of 80%-98%. The dual staining in combination with urine cytology showed comparatively higher sensitivity and specificity in the range of 70%-90% and 74%-100%, respectively. This was more evident for high-grade UC (HGUC). Overall, single or dual staining combined with urine cytology was effective in this detection and can be applied as an adjunct marker in urine cytology.