The Slit-Robo pathway has shown to be altered in several malignant diseases. However,
its role in bladder cancer is poorly understood. Therefore, we aimed to assess the
tissue expression of Robo1 and Robo4 as well as their ligand Slit2 in different stages
of bladder cancer to explore possible changes of Slit-Robo signalling during the progression
of bladder cancer. Robo1, Robo4 and Slit2 gene expressions were analyzed in 92 frozen
bladder cancer tissue samples by using reverse transcription quantitative real-time
PCR. Immunohistochemical analyses were performed on 149 formalin-fixed and paraffin-embedded
bladder cancer tissue samples. Results were correlated with the clinical and follow-up
data by performing both univariable and multivariable analyses. Robo1 and Robo4 nuclear
staining intensitiy was significantly higher in low stage and low grade bladder cancer.
Elevated Robo1 nuclear staining was associated with better disease-specific survival
(DSS) (p = 0.045). Similarly, stronger Robo4 nuclear staining tended to be associated
with longer DSS (p = 0.061). We found higher Robo1 and Slit2 gene expression levels
in advanced stages of bladder cancer (p = 0.007 and p < 0.001). High Slit2 gene expression
was correlated with significantly shorter DSS (p < 0.005), while Robo1 and Robo4 gene
expressions were not associated with patients' prognosis. Our results demonstrate
that the nuclear expression of Robo1 and Robo4 is associated with a favourable prognosis
suggesting that its translocation into the nucleus represent a posttranslational regulation
process which may exhibit an antitumor effect in bladder cancer.
