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Open Access Research article

Serial detection of circulating tumour cells by reverse transcriptase-polymerase chain reaction assays is a marker for poor outcome in patients with malignant melanoma

Giuseppe Palmieri1*, Sabrina MR Satriano2, Mario Budroni3, Antonio Cossu4, Francesco Tanda4, Sergio Canzanella5, Corrado Caracò2, Ester Simeone2, Antonio Daponte2, Nicola Mozzillo2, Giuseppe Comella2, Giuseppe Castello2 and Paolo A Ascierto2

Author Affiliations

1 Istituto di Chimica Biomolecolare-Consiglio Nazionale Ricerche, Li Punti-Sassari, Italy

2 Istituto Nazionale Tumori "Fondazione Pascale", Napoli, Italy

3 Centro Multizonale di Osservazione Epidemiologica, Azienda U.S.L. 1, Sassari, Italy

4 Servizio di Anatomia Patologica, Azienda U.S.L. 1, Sassari, Italy

5 Associazione House Hospital Onlus, Napoli, Italy

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BMC Cancer 2006, 6:266  doi:10.1186/1471-2407-6-266

Published: 15 November 2006

Abstract

Background

Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM).

Methods

One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up.

Results

Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (≥2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage.

Conclusion

Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease.