Utility of Smo as a Prognostic Marker for Human Bladder Tumors / 대한비뇨기과학회지

ABSTRACT

PURPOSE: Smoothened(Smo) encodes a 1,024 amino acid transmembrane protein that acts as a transducer of the hedgehog(Hh) signal and maps to 7q31-q32 in humans. In the absence of Hh, Patched(Ptc) prevents Smo from signaling. When M-Hh-N binds to Ptc, however, Smo is free to upregulate downstream genes in the network. Activating mutations in Smo have been identified in sporadic basal cell carcinomas. This study was performed to evaluate the significance of Smo expression in humanzbladder cancer. MATERIALS AND METHODS: Tumor tissues were obtained from 140 patients with bladder cancer and normal bladder mucosa were acquired from 17 patients without bladder cancer as controls. Smo expression was assessed from paraffin sections of tissues using immunohistochemistry and graded on a scale of 0-12 according to the intensity and rate of staining. Differences of Smo expression between the bladder tumors and normal mucosa were compared. The relationships between their expression and the pathological or clinical characteristics such as tumor stage, grade, recurrence, and progression were also analyzed. RESULTS: There was no difference in the Smo expression in comparisons between the bladder cancers and the normal tissues(4.96+/-1.92 vs.4.52+/-0.87, p=0.111). Superficial bladder tumors had a higher Smo expression compared with normal tissues(0.005). Smo expression in the superficial and low-grade bladder tumors were higher than in the invasive and high-grade bladder tumors(p=0.002 and 0.001, respectively). The progression status was correlated with Smo expression but not the recurrence status(p=0.041 and 0.357, respectively). However, the Smo expression levels were not associated with the overall survival of patients(p=0.406). CONCLUSIONS: The results of this study showed that the enhanced expression of Smo was correlated with superficial, low-grade bladder cancer and tumors without progression. These results suggest that Smo is closely correlated with the differentiation and progression of bladder cancer and may, therefore, be useful as a prognostic marker for bladder cancer in the clinical setting.