BERKELEY, CA (UroToday.com) - While early cystectomy is indicated in select patients with polychronotropic stage Ta, T1, and CIS bladder cancer, the standard of care to prevent tumor progression for these patients continues to be intravesical BCG. Identifying genetic or immunohistochemical markers predicting tumor invasiveness would greatly augment our ability to select patients for early cystectomy.

In the May 1st issue of Clinical Cancer Research, Kader, Wu and colleagues from the M.D. Anderson Cancer Center report on a study designed to evaluate the relationship between MMP polymorphisms and bladder cancer invasiveness in smokers and non-smokers.

A total of 11 single-nucleotide polymorphisms and one microsatellite polymorphism in MMP genes MMP1, MMP2, MMP3, MMP8, MMP9, and MMP12 were evaluated. The cohort consisted of 243 Caucasian patients with muscle invasive bladder cancer and 315 Caucasian patients with non-muscle invasive disease.

The expressions of the MMP9 microsatellite ? 24 CA repeat and MMP12 -82 G alleles were independently associated with a higher risk of tumor invasiveness (odds ratio = 3.10; 95% CI 1.17 to 8.23 and OR = 1.50; 95% CI, 1.00 to 2.28, respectively). This association was found to be even stronger in patients with a history of smoking (5.16-fold risk of invasiveness for MMP9).

This well-conducted bench-to-bedside study is the first to suggest that genetic changes in matrix metalloproteinase expression may contribute to bladder cancer invasiveness. Additional studies are in progress to correlate MMP polymorphism expression and the risk of tumor progression in patients with Ta and T1 tumors treated with intravesical therapy.

Karim Kader, Jun Liu, Lina Shao, Colin P. Dinney, Jie Lin, Yunfei Wang, Jian Gu, H. Barton Grossman, and Xifeng Wu

Clin Cancer Res. 2007 May 1; 13(9):2614-20.

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Written by Ricardo Sånchez-Ortiz, MD, a Contributing Editor with UroToday.

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