Prognostic Value of Circulating Melanoma Cells Detected by Reverse Transcriptase–Polymerase Chain Reaction

Abstract

Detection of CMCs in peripheral blood samples at the time of MM diagnosis by semiquantitative RT-PCR does not add any significant predictive value to the stage of disease. Thus, this approach should not be used in clinical practice, and further studies are required to determine its usefulness.

Prognostic Value of Multiple Reverse Transcription-PCR Tyrosinase Testing for Circulating Neoplastic Cells in Malignant Melanoma

“…In the majority of published studies, results indicated that TYR-positive patients have a higher risk of recurrence of disease (7, 9 -11, 14, 15, 17, 19 -21 ) and a lower probability of overall survival (8, 11, 18, 20 -24 ). However, other investigators raised doubts concerning the clinical value of monitoring MM progression with use of the TYR test because they found no relationship between positive TYR results and diseasefree and overall survival (13,17,(25)(26)(27)(28).…”

Circulating Serologic and Molecular Biomarkers in Malignant Melanoma

“…67,68 Patients with circulating tumor cells have been shown to have inferior survival, 69 but some investigators have found that circulating melanoma cells add little prognostic value beyond that defined by disease stage. 70 If present in circulation, the tumor cells are usually in extremely minute concentrations. Reverse transcription-polymerase chain reaction (RT-PCR) has allowed exponential amplification of messenger RNAs (mRNAs) encoding different proteins associated with the melanoma cell, providing a highly sensitive method of detection.…”

Circulating Melanoma Cells

“…From these results it is obvious that; a) CTCs are present at relatively low concentrations; one tumour cell per 10 6 to 10 7 normal blood cells or on average, 1 cell per ml of blood 69,70,71 ; b) the number of cells appears to be related to stage 2,25,72 ; c) melanoma cell markers differ with respect to stage 73 ; and c) CTC gene expression differs from that of the primary tumour 28,29 . Quantitative RT-PCR has typically detected expression of melanocytic genes such as tyrosinase (TYR) 74,75 since normal melanocytes are not thought to circulate in peripheral blood and therefore detection of transcripts from melanocytic genes should correlate to identification of CTCs 72,76 . The sensitivity and specificity of PCR for circulating melanoma cells is increased by analysis of multiple markers 76 , and these commonly include melan-A (MLANA), beta-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), silver homolog (SILV), melanoma cell adhesion molecule (MCAM), melanoma associated antigen p97 (MFI2), melanoma antigen family A3 (MAGEA3) and microphthalmia-associated transcription factor 4 (MITF4) 63,64,77,78 .…”