Molecular detection of micrometastases and circulating tumor cells in melanoma prostatic and breast carcinomas

The molecular detection of circulating tumor cells (CTC) and micrometastases may help develop new prognostic markers in patients with solid tumors. In the last 10 years, numerous groups have attempted the detection of occult tumor cells in solid malignancies using the highly sensitive reverse transcriptase polymerase chain reaction (RT PCR) technique. These assays were in the vast majority directed against tissue specific markers. In most studies on prostatic carcinoma, RT PCR was able to specifically detect prostatic tissue specific markers in the peripheral blood (PB), bone marrow (BM) and lymph nodes of patients with localized and metastatic disease. Melanoma related transcripts were detected by RT PCR in the PB, BM and lymph nodes of patients with localized and advanced tumors. In most studies, melanoma related markers were shown to be specific except when assayed in lymph nodes. RT PCR positivity rates were highly variable between studies. Despite tFlese discrepancies, many authors have shown a statistically significant correlation between RT PCR positivity and a poorer outcome in both melanoma and prostatic carcinoma. In breast carcinoma, all markers that have been extensively tested were shown to be non-specific. Because of the many limitations of RT PCR (e.g. false positives), many groups are developing new approaches for the detection occult tumor cells. One of these techniques involves immunobead isolation of CTC and micrometastases prior to down stream analysis. The tumor rich magnetic fraction can be subjected to RT PCR, immunocytochemistry and flow cytometry. In conclusion, the molecular detection of occult tumor cells in solid tumors seems very promising and the techniques used for this purpose are in continuous evolution. Large prospective and interlaboratory variability studies are necessary to determine the accuracy and prognostic value of these assays.