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

Study Type – Aetiology (case control) Level of Evidence 3b What’s known on the subject? and What does the study add? A number of studies have reported several clinicopathological factors closely associated with intravesical recurrence of non-muscle invasive bladder cancer (NMIBC). In addition, various types of molecular markers have been shown to be useful for predicting intravesical recurrence of NMIBC following transurethral resection (TUR). Of six subunits of integrin proteins, including α2, α3, α5, α6, β1 and β4, the expression level of the β4 subunit in NMIBC, in addition to pathological T stage and concomitant carcinoma in situ appeared to be independently related to intravesical recurrence. Therefore, consideration of the expression levels of integrins, particularly that of the β4 subunit, in TUR specimens would contribute to further accurate prediction of intravesical recurrence of NMIBC. 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, β1 and β4, were measured in TUR specimens by immunohistochemical staining. RESULTS •  Of the six proteins, expression levels of α2-, α3-, α6- and β4-subunits were significantly associated with the incidence of intravesical recurrence. Univariate analysis identified expression levels of α3-, α6- and β4-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 β4 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 β4 subunit, in TUR specimens, in addition to conventional variables, would contribute to accurate prediction of intravesical recurrence after TUR for NMIBC patients.