Utility of ProEx C in the histologic evaluation of the neoplastic and nonneoplastic urothelial lesions

SummaryProEx C is an antibody cocktail targeting the expression of topoisomerase IIα and minichromosome maintenance protein 2. ProEx C staining is being used mainly to assist in diagnoses of dysplasia in gynecological specimens. This study was designed to determine the utility of ProEx C in assessing the urothelial lesions. Sixty-four patient specimens were divided into 5 groups: group I, 22 benign; group II, 13 low-grade noninvasive papillary urothelial carcinoma; group III, 10 high-grade urothelial carcinoma in situ (flat lesion); and group IV, 19 high-grade noninvasive papillary and invasive urothelial carcinomas. ProEx C reactions were scored in basal, parabasal, intermediate, and superficial cell layers. A sample was recorded as positive when nuclear staining was seen in the cells of the intermediate and/or superficial layers. Of 22 cases in group I, 21 were negative for ProEx C with a specificity of 95%. Of 13 cases in group II, 11 had positive results with sensitivity of 85%. All cases in groups III and IV had positive staining pattern with ProEx C with a sensitivity of 100%. In this study, ProEx C stain had an overall 95% sensitivity and specificity with positive and negative predictive values of 98% and 91%, respectively, for detection of urothelial carcinoma. We conclude that ProEx C is effective in differentiating carcinoma in situ and benign urothelial lesions. It also resolves issues in low- versus high-grade papillary urothelial carcinomas. To our knowledge, this is the first publication on the diagnostic application of ProEx C in histopathology of the urothelial lesions.