Evaluation of a Triple Combination of CK20, p53 and CD44 for Improving Detection of Urothelial Carcinoma in Urine Cytology Specimens.
Brent Arville, Emily O'Rourke, Fai Chung, Mahul B Amin, Shikha Bose. Cedars-Sinai Medical Center, Los Angeles, CA
Background: Expression of CK20, CD44, and p53 have been shown to be useful in differentiating high grade urothelial lesions (CK20+, p53+) from low grade lesions including reactive atypia (CD44+) in surgical specimens. Most urine cytology specimens diagnosed as "atypical" trigger cystoscopy with additional sampling or testing for molecular abnormalities with the Urovision FISH test, both of which increase cost and patient discomfort. Cytology material is generally limited and restricts the use of multiple immunostains. This study was designed to determine the utility of a cocktail of the three stains, CK20, p53, and CD44 (TSC), in urine cytology samples for improving the detection of urothelial carcinoma.
Design: 73 urine cytology specimens (22 negative, 42 atypical, and 9 positive cases) with adequate cellular material on cell blocks were retrieved from the department files between 2007-2010. Smears were screened to confirm adequacy and cytologic diagnosis. 51/73 (69.9%) cases had surgical biopsy and/or FISH testing concurrently or within 6 months of diagnosis. IHC staining with the TSC cocktail was obtained on the cell block for all 73 cases. Positive staining was visualized as red cytoplasmic (CK20), brown membranous (CD44), and brown nuclear (p53). TSC was recorded as positive when CK20 and/or p53 staining was seen in morphologically atypical urothelial cells and as negative if no staining was observed or only CD44 staining was seen.
Results: A positive TSC stain had a sensitivity of 80%, specificity of 92.3%, PPV of 90.9% and NPV of 82.8% for the detection of urothelial carcinoma.
|Cytologic diagnosis (n=73)|
|Negative (n=22)||atypical (n=42)||Positive (n=9)|
|Negative cytology (n=15)||Atypical cytology (n=28)||Positive cytology (n=8)|
|Negative follow-up||Positive follow-up||Negative follow-up||Positive follow-up||Negative follow-up||Positive follow-up|