RESUMO
BACKGROUND: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). METHODS: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. RESULTS: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). CONCLUSION: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.
Assuntos
Biomarcadores Tumorais/genética , Interleucina-8/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Proteínas Ligadas por GPI/genética , Perfilação da Expressão Gênica , Humanos , Interleucina-8/genética , Masculino , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Inibidores Teciduais de Metaloproteinases/genéticaRESUMO
BACKGROUND: The purpose of this study was to compare the efficacy of 2 bacillus Calmette-Guérin (BCG) strains, BCG-Tice and BCG-Moreau, in the treatment of non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively reviewed clinical data from patients treated with BCG for NMIBC at 3 academic centers. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare recurrence-free (RFS) and progression-free survival (PFS) of patients in the 2 treatment groups. In addition, we performed exploratory analyses of treatment effect according to the receipt of adequate BCG treatment, high-risk disease, age, gender, smoking status, pathologic stage, and pathologic grade. RESULTS: A total of 321 (48.6%) patients were treated with BCG-Tice and 339 (51.4%) with BCG-Moreau. IPTW-adjusted Cox proportional hazard regression analysis did not show a difference in RFS (hazard ratio, 0.88; 95% confidence interval, 0.56-1.38; P = .58) or PFS (hazard ratio, 0.55; 95% confidence interval, 0.25-1.21, P = .14) between BCG-Tice and BCG-Moreau. On subgroup analyses, we could not identify an association of BCG strain with outcomes. CONCLUSIONS: There was no difference in RFS and PFS between BCG-Tice and BCG-Moreau strains in the adjuvant treatment of NMIBC. However, we confirmed the importance of maintenance therapy for achieving a sustainable response in patients with intermediate- and high-risk NMIBC.