Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium - An analysis of cytokeratin 20, p53, and CD44 antigens

Distinction of urothelial carcinoma in situ (CIS) from reactive atypia on t he basis of morphology alone may be difficult in some cases. Because this d istinction is therapeutically and prognostically critical, we attempted to determine if an immunohistochemical panel would help in this differential d iagnosis. The immunoprofile of 21 cases of CIS and 25 non-neoplastic urothe lia (15 urothelial biopsies with reactive atypia from patients without a hi story of bladder cancer and 10 normal ureter sections from nephrectomies pe rformed for renal cell carcinoma) was determined using antibodies against c ytokeratin 20 (CK20), p53, and CD44 (standard isoform). In the normal uroth elium CK20 showed patchy cytoplasmic immunoreactivity in only the superfici al umbrella cell layer and CD44 stained only the basal cells. Nuclear immun oreactivity to p53 varied from negative to weak and patchy. Reactive urothe lium also showed CK20 immunoreactivity in only the umbrella cell layer in a ll 15 cases, and p53 nuclear staining was predominantly negative with occas ional weak positivity in the basal and parabasal intermediate cells. CD44 w as overexpressed in the entire reactive urothelium in 9 cases (60%) or foca lly positive in intermediate cells in 6 cases (40%). In contrast, CIS showe d intense CK20 and p53 positivity (81% and 57%, respectively) in the majori ty (>50%) of malignant cells. CD44 staining revealed residual basal cells w ith membranous reactivity in 44% of the cases of CIS; however, the neoplast ic cells were immunonegative in all cases. At least one positive immunomark er (CK20 or p53) was abnormally expressed in all cases of CIS. Abnormal exp ression of CK20 (increased), p53 (increased), and CD44 (decreased) in uroth elial CIS, and increased expression of CD44 in reactive atypia allows more confident distinction of urothelial CIS from non-neoplastic urothelial atyp ias. From a differential diagnosis perspective, use of a panel of all three antibodies with morphologic correlation would be essential.