Abstract
BackgroundDetection 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).MethodsOne 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.ResultsDetection 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.ConclusionOur 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.
Highlights
Detection of circulating malignant cells (CMCs) through a reverse transcriptasepolymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease
Tyrosinase (TYR), an enzyme that is involved in the melanin biosynthesis pathway [8], is the marker most frequently used to detect the presence of CMC in melanoma patients; its clinical usefulness is highly debated [9,10,11,12,13]
Staging was according to the recent American Joint Committee on Cancer (AJCC) guidelines
Summary
Detection of circulating malignant cells (CMCs) through a reverse transcriptasepolymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. To improve sensitivity and specificity of the procedure, we and others have previously proposed a multi-marker RTPCR assay, including melanA/MART1 in addition to tyrosinase (the use of TYR mRNA as unique marker could be of limited value in the management of MM patients, due to the heterogeneity of TYR expression in melanomas) [14,15,16,17,18] Such a multi-marker RT-PCR assay has been demonstrated to really improve the detection of melanomaassociated transcripts in peripheral blood of patients who have undergone radical surgery [7,14,15]. Detection of minimal residual disease at the time of diagnosis by RTPCR seems to be correlated with the initial clinical stage; our group has demonstrated that it does not add any power to the predictive value of the disease stage [19]
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