Prognostic value of microphthalmia-associated transcription factor and tyrosinase as markers for circulating tumor cells detection in patients with melanoma
Abstract:The aim of this study was to analyze microphthalmia-associated transcription factor (MITF) as a marker for the detection of circulating melanoma cells, determine its prognostic value in melanoma patients, and compare it with tyrosinase. Blood samples from 201 melanoma patients in all stages of the disease and 40 healthy volunteers were analyzed. RNA was isolated from mononuclear cell fraction of the blood and assayed by reverse transcription-PCR for the expression of MITF and tyrosinase. All samples from healt… Show more
“…Its detection after treatment is, in fact, a significant independent prognostic indicator for the patients' survival [25]. When it was assayed by RT-PCR along with TYR and MITF transcripts, an increase in the detection rate of CMCs, from 25% to 38% for stages III and IV, respectively, was found [26].…”
“…Its detection after treatment is, in fact, a significant independent prognostic indicator for the patients' survival [25]. When it was assayed by RT-PCR along with TYR and MITF transcripts, an increase in the detection rate of CMCs, from 25% to 38% for stages III and IV, respectively, was found [26].…”
“…Nevertheless, several studies have shown the detection of CMC may represent a biomarker that can identify metastatic disease spread. [8, 9, 11, 13, 16–18, 21, 24–26, 40–43] Polymerase chain reaction (PCR)-based techniques have been used to monitor CMCs for treatment response in metastatic melanoma patients receiving chemotherapy and biochemotherapy. [12, 14, 15, 20, 22, 23] However, the reproducibility of PCR-based detection methods is low,[44, 45] which hinders their reliability and implementation in routine clinical practice.…”
Objectives
Significant prognostic heterogeneity exists within the sub-stages of melanoma; therefore, novel prognostic biomarkers are needed to provide information regarding recurrence risk. Limited available data suggests prognostic significance for circulating melanoma cells (CMCs); there is a need for a sensitive, reproducible, and standardized identification technique. Using a semi-automated technology, we sought to determine whether CMCs could reliably be identified in stage I–IV melanoma patients and if CMC presence correlated with known prognostic factors.
Methods
CMCs were detected in the peripheral blood (7.5cc) of patients with stage I–IV melanoma (n=89) using the CellSearch® system (Janssen, Raritan NJ). CD146+ cells were immunomagnetically enriched; nucleated HMW-MAA+/CD45−/CD34− cells were considered CMCs.
Results
One or more CMCs was detected in 45% of all patients, varying with stage of disease (Stages I /II, III, and IV: 35%, 44%, and 86%, respectively; p=0.03, for stage I/II vs. stage IV); 55% had one CMC, 32% had two CMCs and 13% had three or more CMCs identified. The presence of CMCs in the blood was associated with histologic subtype, particularly in patients with Stage I /II disease (superficial spreading 18% vs. acral lentiginous 75%).
Conclusions
Using a semi-automated technique, CMCs can be identified in a significant number of melanoma patients. These data support further study with longer follow-up and longitudinal/serial time points to better determine the identification rates and prognostic significance of CMCs in stage I–IV melanoma patients.
“…Because MCAM promotes progression, it is associated with a more aggressive phenotype and more advanced disease. Alternatively, CMC can be purified by negative selection by lymphocyte depletion with [55,57,71] anti-CD45 antibody [66]. This approach is independent of malignant cell characteristics and appears to have better recovery versus positive selection methods [48].…”
Section: Methods For Circulating Melanoma Cell Enrichment and Detectionmentioning
confidence: 98%
“…To increase CMC detection rate, tyrosinase mRNA has been combined with other mRNA targets [84]. These include melanoma antigen recognized by T-cells (Melan-A/MART-1) [36], microphthalmia-associated transcription factor (MITF) [55], gp100, MAGE-3 [61], and p97 (melanotransferrin) ( Table 2).…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.