Utility of Triple Combination Immunohistochemical (IHC) Stain "Uro3" (CK20/CD44/p53) in the Distinction of Urothelial Carcinoma In Situ (CIS) from Its Mimics
RS Parakh, DJ Luthringer, JK McKenney, DE Hansel, DE Westfall, M Vankalakunti, R Alsabeh, MB Amin. Cedars- Sinai Medical Center, Los Angeles, CA; Stanford School of Medicine, Stanford, CA; Cleveland Clinic, Cleveland, OH
Background: CIS is a prognostically and therapeutically significant lesion with considerable morphologic overlap with reactive conditions; the diagnostic difficulty is compounded in the setting of prior therapy. The utility of CK20, CD44 and p53 IHC has been reported, however its value in post-treatment scenario is not fully established.Herein we evaluate the use of URO3, a triple antibody cocktail (CK20/p53/CD44), as a tool for detecting expression of all three markers in a single bladder biopsy section.
Design: Sixty-five bladder biopsies [14 CIS; 17 benign/reactive urothelium; 9 post-radiation with reactive atypia(8) or CIS(1); 11 cases of normal/reactive urothelium post BCG treatment; 11 CIS post-BCG treatment, 3 CIS post-mitomycin/systemic therapy showing reactive(1), "highly atypical but not diagnostic"(1) and CIS(1)] were evaluated. The URO3 cocktail consisted of brown nuclear p53 (clone DO7), brown membranous CD44 (clone MRQ-13) and red cytoplasmic and membranous CK20 (clone Ks20.8). Three staining patterns were evaluated: "URO3 -malignant" (full thickness CK20+/-, full thickness p53+/- and CD44-), "URO3-reactive" (full thickness CK20 and p53- and CD44+ basal to full thickness) and "indeterminate URO3" (CK20 and p53+/- not full thickness and/or CD44+).
Results: CIS without history of prior treatment showed URO3-malignant in 93% and URO3-reactive in 7%. CIS with history of prior treatment showed URO3-malignant in 77%, URO3-reactive in 15% and indeterminate-URO3 in 8%. Benign or reactive urothelium showed URO3- reactive pattern in 100%. Benign or reactive atypia after treatment showed URO3-reactive in 86% and indeterminate-URO3 in 14%; no case showed URO3-malignant pattern.
Conclusions: 1) Our data suggests diagnostic utility of the URO3 cocktail (CK20, p53, and CD44) in the distinction of CIS from reactive/regenerative urothelium in the pre- and post- treatment settings. 2) Simultaneous evaluation of all three markers in a single slide (URO3) is advantageous, as the overall immunoprofile is more useful than for any of individual marker; multiplexing is further valuable in small biopsy specimens where tissue may be lost in subsequent levels for IHC.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 133, Monday Morning