Analysis of Matrix Metalloproteinase Expression in the Recurrence of Superficial Low Grade Urothelial Bladder Cancer

Abstract

Purpose: Superficial bladder transitional cell carcinomas (TCCa) have high recurrence rates following endoscopic resection. Most of the parameters used for the prediction of a recurrence are associated with high grade TCCa. However, there are few valid parameters for prediction of the recurrence of low grade TCCa. We aimed to elucidate the prime factor of a recurrence of superficial low grade bladder TCCa. Materials and Methods: Thirty cases of superficial low grade bladder TCCa were analyzed, 15 of which were recurred cases. Fresh frozen tumor and normal tissues were used for the analysis. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blots analyses were subsequently performed to evaluate the validity of the molecules identified by a 0.12K cDNA array, including matrix metalloproteinase (MMP), oncogenes and cell-cycle-related genes. Results: On cDNA microarray analysis, MMP-1, 2, 9, 12 and 15, and transforming growth factor beta1 (TGFbeta1), vascular endothelial growth factor (VEGF) and fos were found to be significantly upregulated in the recurred cases. From the real-time RT-PCR for the validation of those molecules, MMP-1 and 12, and TGFbeta1, VEGF and fos were significantly overexpressed in the recurred cases. Western blot showed significant overexpression of MMP-1 and 12, and TGFbeta1, VEGF and fos in the recurred cases. Conclusions: The overexpressions of MMP-1 and 12, and TGFbeta1, VEGF and fos may be associated with the recurrence of superficial low grade bladder TCCa.