The Role of Immunohistochemistry in the Diagnosis of Flat Urothelial Lesions: A Study Using CK20, CK5/6, P53, CD138, and HER2/Neu
Sungmi Jung, Chenbo Wu, Zohreh Islami, Simon Tanguay, Armen Aprikian, Wassim Kassouf, Fadi Brimo. McGill University Health Center, Montreal, QC, Canada
Background: Although differentiating reactive urothelial atypia from urothelial carcinoma in situ (CIS) relies primarily on histological evaluation, confirming the morphologic impression using immunohistochemistry (IHC) has been increasingly used in routine practice, especially in small biopsy specimens. We aimed to confirm the utility of commonly used markers (CK20, P53) and to test the performance of CK5/6, CD138, and HER2/neu in the diagnosis of CIS.
Design: Using a TMA comprised of 52 cases of normal/reactive urothelium (from bladder and prostatic urethra) and 45 cases of CIS, the IHC evaluation of the five markers was undergone. The following staining patterns were considered positive for a diagnosis of CIS and different patterns of staining were considered negative: CK20 (+) moderate to strong staining in atypical cells (usually full thickness); P53(+) moderate to strong staining in atypical cells (usually full thickness); Her2/neu(+) strong staining (+2 +3) in atypical cells (usually full thickness); CD138 (+) moderate to strong staining in atypical cells; CK5/6(+) negative staining or staining restriced to basal/parabasal cells.
Results: The discriminatory performance of CK5/6 and CD138 was poor. Although the individual specificity of CK20, P53, and HER2/neu was high (94%, 90%, and 93%, respectively), their sensitivity for CIS detection was lower with the most sensitive marker being Her2/neu (63%). Whereas 65% of CIS showed positivity for ≥2 of those 3 markers, only one case of reactive urothelium was positive for 2/3 antibodies.
|Antibody||Result||Urothelial carcinoma in situ||Non-neoplastic urothelium||Sensitivity (%)||Specificity (%)|