Utility of Minichromosome Maintenance Protein 2 (MCM 2) and Topoisomerase II-alpha (TOP2A) Immunohistochemical Staining in the Diagnosis of Neoplastic and Non-Neoplastic Urothelial Lesions
Susan Kerkoutian, Jian Yu Rao, Sophia K Apple, David Lu, Gretchen Galliano, Neda A Moatamed. University of California Los Angeles, Los Angeles, CA
Background: Occasionally, morphologic distinction of neoplasia or dysplasia from reactive changes in the bladder can be challenging. ProEx C is a novel biomarker cocktail containing antibodies against topoisomerase II alpha and minichromosome maintenance protein 2. These two proteins are overexpressed in the cell nucleus during aberrant S-phase induction of the neoplastic cells and in HPV infected cells. Studies have demonstrated the utility of ProEx C as an adjunct marker for assessing dysplasia in gynecologic specimens and cervical smears. The goal of this study is to evaluate the utility of ProEx C as an adjunct marker in distinguishing neoplastic and non-neoplastic urothelial lesions.
Design: Sixty-four bladder biopsy or cystectomy specimens were evaluated (29 high grade urothelial carcinoma (HGUC) including 4 carcinoma in situ (CIS), 13 low grade papillary urothelial carcinoma (LGPUC), and 22 benign/denuded). Four-micrometer thick serial sections of formalin-fixed, paraffin-embedded tissue were cut and mounted on positively charged glass slides. Immunohistochemical staining for ProEx C with appropriate positive and negative controls was performed. A nuclear staining pattern which extended above one-half of the thickness of urothelium or more than 10% of the cells was scored as positive. No staining, staining at the base of the urothelium, or less than 10% staining of the cells was scored as negative.
Results: All of the benign/denuded cases (0/22) stained negative for Pro Ex C. All of the HGUC and carcinoma in situ (CIS) cases (29/29) stained positive. Most of the LGPUC cases (11/13) stained positive for Pro Ex C. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for ProEx C immunostaining were 95.2%, 100%, 100%, and 91.7%, respectively.