Association of cyclin D1 and E1 expression with disease progression and biomarkers in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder

PURPOSE: To determine the association of cyclin D1 and E1 expression with bladder cancer presence, clinical and molecular characteristics, and disease progression in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder. METHODS: Immunohistochemical staining for cyclin D1, cyclin E1, p53, p21, p27, pRB, KI-67, and survivin was performed on a tissue microarray containing specimens from 9 normal controls and 74 patients with Ta, Tis, and/or T1 urothelial cell carcinoma of the bladder. Cyclin D1 and E1 immunoreactivity were considered low when samples showed less than 10% and 30% nuclear reactivity, respectively. RESULTS: Normal bladder urothelium from all 9 control patients showed uniformly intense expression of cyclin D1 and cyclin E1. Cyclin D1 and E1 expression were low in 23 of 74 (31.1%) and 27 of 74 (36.5%) specimens. Kaplan-Meier analyses showed that low expression of cyclin E1 was significantly associated with an increased probability of tumor recurrence and progression in univariate, but not multivariate analysis. Cyclin D1 immunoreactivity was not associated with any pathologic characteristics or clinical outcomes. Low cyclin E1 expression was significantly associated with altered expression of p53, pRB, KI-67, and survivin. CONCLUSIONS: Tissue expression of cyclin D1 or E1 seems not to add independent prognostic value to standard features in patients with nonmuscle -invasive urothelial cell carcinoma of the bladder.