Micrometastases may be defined as the presence of cancer cells detected by molecular techniques in patients with no demonstratable evidence of disease by conventional radiographic and pathologic staging. To date, the detection of micrometastases in bladder cancer has primarily involved evaluating the expression of several urothelial-marker genes from the lymph nodes, serum, and bone marrow of patients with urothelial carcinoma. Uroplakin II (UP II) has been the most widely investigated of these genes, as UP II mRNA expression has been consistently detected in lymph nodes considered to be negative for carcinoma by conventional histology. UP II expression has thus shown promise as a molecular marker of micrometastatic disease, although correlation with patient outcome has been limited, and thus the ability to determine the clinical significance of detecting such molecular, or micro-metastases remains to be established.
In addition to detecting micrometastases, efforts have also been made to predict the presence of micrometastases in patients with urothelial cancer, based on the molecular characteristics of the primary bladder tumor. Here, investigators have focused mainly on evaluating the expression of cell-cycle regulatory genes, specifically the p53 and retinoblastoma (pRb) genes. The expression of these targets in primary bladder tumors has been found to correlate with disease recurrence and patient survival, independent of tumor stage, grade, and nodal status, suggesting their potential role as molecular predictors of micrometastatic disease. Future efforts are likely to utilize high-throughput techniques such as proteomics and microarrays to determine patients' risk of disease progression from the molecular expression pattern of the primary tumor. Here, we review the current status of the detection, prediction, and clinical significance of micrometastases in bladder cancer.