Molecular detection and characterization of circulating tumor cells and micrometastases in prostatic, urothelial, and renal cell carcinomas.

Abstract

The detection and molecular characterization of circulating tumor cells (CTCs) and micrometastases in urinary tract and prostatic tumors may have important prognostic and therapeutic implications. In the last decade, numerous groups have attempted the detection of occult tumor cells in renal, prostatic, and urothelial carcinomas using the highly sensitive reverse-transcriptase polymerase chain reaction (RT-PCR). In prostatic carcinoma (PC), tissue-specific transcripts were detected with high specificity in the blood of patients with localized and advanced disease. PCR assays for PC detection were shown to be strong predictors of poorer outcome in some reports, while a lack of prognostic significance was found in other studies. There was a vast difference in the PCR positivity rates between various groups studying PC. This discrepancy could be due to variations in PCR methodology. In urothelial and renal cell carcinoma, the amount of research on the subject is still too limited. Currently, these assays for occult tumor cells are promising but are not yet ready to use in PC and urinary tract tumors. Because of the many limitations of PCR (e.g., false positives), many groups are developing new approaches for the detection of occult tumor cells. The most attractive technique involves immunomagnetic isolation of intact CTC and micrometastases prior to downstream analysis. The tumor-rich magnetic fraction can be subjected to RT-PCR, immunocytochemistry, and in situ hybridization. This will lead to better quantification and molecular characterization of these tumor cells.