Molecular detection and characterisation of circulating tumour cells and micrometastases in solid tumours

The detection and molecular characterisation of circulating tumour cells (CTC) and micrometastases may have important prognostic and therapeutic implications. Because their numbers are very small, these tumour cells are not easily detected using conventional methods. In the last decade, numerous groups have attempted to detect occult tumour cells in solid malignancies using the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR). These assays were in the vast majority directed against tissue-specific markers. PCR was shown to be superior to conventional techniques in detecting occult tumour cells allowing the identification of one malignant cell mixed with 1-10 million normal cells. In some tumours like melanoma and prostatic carcinoma, tissue-specific transcripts were detected with high specificity in the blood of patients with localised and advanced disease. In some reports, PCR was shown to be a strong predictor of poorer outcome. However, due to the many limitations of PCR (e.g false-positives), many groups are developing new approaches for the detection of occult tumour cells. The most attractive technique involves immunomagnetic isolation of CTC and micrometastases prior to downstream analysis. The tumour-rich magnetic fraction can be subjected to RT-PCR, immunocytochemistry and in situ hybridisation. This will lead to better quantification and molecular characterisation of these tumour cells. In conclusion, the molecular detection and characterisation of occult tumour cells offer a great opportunity for better stratifying patients with solid tumours and for developing new prognostic markers and targeted therapies.