Effects of Transforming Growth Factor-beta1 and Its Receptor on the Development, Recurrence and Progression of Human Bladder Cancer / 대한비뇨기과학회지

ABSTRACT

PURPOSE: We investigated whether the expression levels of Transforming growth factor beta1 (TGF-beta1) and its receptors were related to the development, recurrence, progression and disease-free survival in the patients with bladder cancer. MATERIALS AND METHODS: The mRNA levels of TGF-beta1 and its receptors were examined in 102 tumor specimens from patients with primary bladder cancer, 29 corresponding normal bladder mucosae specimens surrounding these tumors and 15 normal bladder mucosae specimens by performing quantitative competitive PCR (QC-PCR). The protein levels of TGF-beta1 and its receptors were investigated by performing immunohistochemical staining on sections cut from 86 archival bladder tissue paraffin blocks. RESULTS: QC-PCR analysis showed that expressions of TGF-beta1, TGF-beta receptor I (TGF-betaRI) and receptor II (TGF-betaRII) in the superficial and low-grade bladder cancers were significantly higher than those in both the corresponding normal bladder mucosae surrounding the cancer (p= 0.0069, 0.0022 and 0.0046, respectively) and the control's normal bladder mucosae (p=0.0014, 0.0125 and 0.0089, respectively). Expressions of TGF-beta1 and its receptors were enhanced in the non-recurred and non-progressed patients compared to the recurred cases (p=0.0022, 0.0003 and 0.0001, respectively) and the progressed cases (p=0.0002, <0.0001 and <0.0001, respectively). Patients with high expression of TGF-beta and its receptors had a significantly higher disease-free survival rate than those patients with low expressions (p=0.0129, 0.0121 and 0.0132, respectively). CONCLUSIONS: The enhanced expression of TGF-beta1 and its receptors was correlated not only with superficial and low-grade bladder cancer, but also with enhanced patient survival. In conclusion, our findings suggest that the expressions of TGF-beta1 and its receptors are useful prognostic markers for a patient's resistance to disease recurrence and/or progression.