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.

Review: polymerase chain reaction detection of micrometastases and circulating tumor cells: application to melanoma, prostate, and thyroid carcinomas.

The main strategy used for the detection of circulating tumor cells (CTC) and micrometastases in solid tumors is the polymerase chain reaction (PCR) amplification of tissue specific messenger RNA present in the tumor cells. PCR was more sensitive than conventional techniques, allowing the identification of one tumor cell diluted into 1 mL of blood. PCR was shown to be specific in most studies related to the detection of CTC and marrow micrometastases in melanoma and prostate carcinoma (PC). PCR positivity for thyroid markers was reported in the blood of control subjects. Large variations in the PCR positivity rates and the prognostic value of these assays have been encountered in PC and melanoma. There was a correlation between PCR and stage in some but not all the studies. Despite these discrepancies, many investigators have shown PCR to be predictive of outcome in PC and especially in melanoma. PCR in blood and bone marrow was an independent predictor of overall and disease-free survival in melanoma patients rendered surgically free of disease. These tests may help better stratify patients for radical surgeries and adjuvant therapy. Large prospective and interlaboratory studies are needed to confirm the accuracy and prognostic value of these assays.