Molecular genetics of urothelial malignancies: Mismatch repair genes as markers for detection and prognosis?

Abstract

Urothelial malignancies were diagnosed in over 50,000 men and women in the United States last year. The majority of these tumors are not muscle invasive and can be treated endoscopically with or without adjuvant intravesical therapy. Cystoscopy and cytology at regular and frequent intervals are essential since many patients experience tumor recurrence, progression or fail to respond to intravesical treatments. Cancer recurrence, progression and intravesical treatment failures can be associated with increased risk of developing metastatic disease if not promptly detected and aggressively treated. Markers that identify patients at increased risk for recurrence, progression and poor response to intravesical therapy would provide useful information in the management of patients with urothelial malignancies. Mismatch repair (MMR) genes are potential markers for detection and prognosis since their expression is linked to tumor predisposition, progression and resistance to chemotherapeutic agents. The molecular biology and biochemistry of MMR will be reviewed and the potential role of human MMR genes for detection, prognosis and treatment of urothelial malignancies will be discussed.