Expression of integrin proteins in non-muscle-invasive bladder cancer: significance of intravesical recurrence after transurethral resection.

OBJECTIVES: • To evaluate the expression of integrin proteins, a family of transmembrane heterodimers, in non-muscle-invasive bladder cancer (NMIBC). • To assess the significance of these proteins as prognostic indicators in patients undergoing transurethral resection (TUR). PATIENTS AND METHODS: • The present study comprised 161 patients diagnosed as having NMIBC after TUR. • Expression levels of six subunits of integrin proteins, including α2, α3, α5, α6, ß1 and ß4, were measured in TUR specimens by immunohistochemical staining. RESULTS: • Of the six proteins, expression levels of α2-, α3-, α6- and ß4-subunits were significantly associated with the incidence of intravesical recurrence. Univariate analysis identified expression levels of α3-, α6- and ß4-subunits as important predictors of intravesical recurrence, while tumour size, pathological T stage and concomitant carcinoma in situ (CIS) were also important. • Multivariate analysis showed that the expression level of the ß4 subunit, pathological T stage and concomitant CIS are independently related to intravesical recurrence. • There were significant differences in intravesical recurrence-free survival for patients who were positive for the three independent risk factors; intravesical recurrence occurred in 10 of 49 (20.4%) patients who were negative for all risk factors, 31 of 68 who were positive for one risk factor (45.6%), and 30 of 44 who were positive for two or three risk factors (68.2%). CONCLUSIONS: • Consideration of the expression levels of integrins, particularly those of the ß4 subunit, in TUR specimens, in addition to conventional variables, would contribute to accurate prediction of intravesical recurrence after TUR for NMIBC patients.

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.