Expression of cell cycle-associated proteins in non-muscle-invasive bladder cancer: Correlation with intravesical recurrence following transurethral resection

The objective of this study was to evaluate the expression patterns of cell cycle-associated proteins in newly diagnosed non-muscle-invasive bladder cancer (NMIBC) to clarify the significance of these proteins as prognostic predictors in 161 consecutive patients undergoing transurethral resection (TUR). Expression levels of 7 cell cycle-associated proteins, including Aurora-A, c-erbB2, cyclin-D1, Ki-67, p21, p27, and p53, in TUR specimens were measured by immunohistochemical staining. Of the 7 proteins, weak expression of p21 was significantly associated with the incidence of intravesical recurrence (P = 0.012). Univariate analysis identified expression level of p21, tumor size, T stage, and concomitant carcinoma in situ (CIS) as significant predictors for intravesical recurrence (P = 0.0053, 0.0014, 0.024, and 0.035, respectively). Of these, p21 expression, tumor size, and concomitant CIS appeared to be independently related to intravesical recurrence (P = 0.029, 0.025, and 0.016, respectively). Furthermore, there were significant differences in intravesical recurrence-free survival according to positive patterns of these 3 independent factors; that is, intravesical recurrence occurred in 17 of 72 patients who were negative for risk factor (23.6%), 30 of 57 positive for a single risk factor (52.6%), and 24 of 32 positive for 2 or 3 risk factors (75.0%). These findings suggest that consideration of expression levels of cell cycle-associated proteins, in addition to conventional parameters, would contribute to accurate prediction of intravesical recurrence following TUR of NMIBC. Moreover, combined evaluation of p21 expression, tumor size, and concomitant CIS might be particularly useful for further refinement of the outcome in predicting intravesical recurrence following TUR of NMIBC.