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Open Access Research article

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

Sabrina Thalita Reis12, Katia Ramos M Leite1, Luís Felipe Piovesan2, José Pontes-Junior12, Nayara Izabel Viana1, Daniel Kanda Abe12, Alexandre Crippa2, Caio Martins Moura1, Sanarelly Pires Adonias2, Miguel Srougi12 and Marcos Francisco Dall’Oglio12*

Author Affiliations

1 Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo, Brazil

2 Uro-Oncology Group, Urology Department, University of Sao Paulo Medical School and Institute of Cancer of State of Sao Paulo (ICESP), Sao Paulo, Brazil

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BMC Urology 2012, 12:18  doi:10.1186/1471-2490-12-18

Published: 13 June 2012

Abstract

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.

Keywords:
Bladder cancer; Matrix metalloproteinase; Prognosis; Diagnosis; Gene expression