Low levels of WWOX protein immunoexpression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours

Aims: To correlate the immunohistochemical detection of WWOX with histological measures and disease progression within the whole spectrum of urothelial bladder neoplasms. Methods and results: One hundred and one patients with primary bladder tumours were retrospectively analysed. Immunohistochemically, a polyclonal antibody was utilized and the level of WWOX protein expression was analysed by using a combined score system based on intensity of the reaction and percentage of immunoreactive tumour cells. WWOX protein expression was consistently expressed in non-neoplastic urothelium, whereas a progressive loss of immunoreactivity was observed as tumour grade and stage increased (P < 0.05). Principal component analysis showed that reduced WWOX immunoexpression was significantly associated with high histological grades (P = 0.001), advanced stage (P = 0.002), tumour size (P = 0.04) and cancer progression (P = 0.028). Invasive urothelial carcinomas of the bladder with squamous metaplasia presented the lowest levels of WWOX protein. Kaplan-Meier analyses demonstrated a significant correlation between loss of WWOX expression and a shorter progression-free survival (P = 0.042), whereas the prediction of overall survival achieved borderline significance (P = 0.053). Conclusion: Loss of WWOX immunoexpression strongly correlates with classical clinicopathological factors and appears to be a potential predictive marker of progressive disease.