Early Detection of Melanoma Progression by Quantitative Real-time RT-PCR Analysis for Multiple Melanoma Markers

Arenberger, Petr; Vohradníková, O; Kremen, J

doi:10.2302/kjm.57.57

Cited by 15 publications

(13 citation statements)

References 34 publications

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“…Already, measurement of tyrosinase mRNA levels was a significant adverse prognostic factor for disease-free survival [25]. Several markers, such as Melan-A, gp100, MAGE-3, melanoma-inhibiting activity (MIA) and tyrosinase were used in the studies by Arenberger et al [26]. Of those, MAGE-3 correlated the best with disease progression.…”

Section: Melanoma Occurrence Staging and Detectionmentioning

confidence: 99%

Current concepts of metastasis in melanoma

Zbytek

Carlson

Granese

et al. 2008

Expert Review of Dermatology

210

188

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The main cause of death in melanoma patients is widespread metastases. Staging of melanoma is based on the primary tumor thickness, ulceration, lymph node and distant metastases. Metastases develop in regional lymph nodes, as satellite or in-transit lesions, or in distant organs. Lymph flow and chemotaxis is responsible for the homing of melanoma cells to different sites. Standard pathologic evaluation of sentinel lymph nodes fails to find occult melanoma in a significant proportion of cases. Detection of small numbers of malignant melanoma cells in these and other sites, such as adjacent to the primary site, bone marrow or the systemic circulation, may be enhanced by immunohistochemistry, reverse transcription PCR, evaluation of lymphatic vessel invasion and proteomics. In the organs to which melanoma cells metastasize, extravasation of melanoma cells is regulated by adhesion molecules, matrix metalloproteases, chemokines and growth factors. Melanoma cells may travel along external vessel lattices. After settling in the metastatic sites, melanoma cells develop mechanisms that protect them against the attack of the immune system. It †Author for correspondence Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, 930 Madison Avenue, Memphis, TN 38163, USA, Tel.: +1 901 448 6300, Fax: +1 901 448 6979, E-mail: aslominski@utmem.edu. Financial & competing interests disclosure:The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. is thought that one of the reasons why melanoma cells are especially resistant to killing is the fact that melanocytes (cells from which melanoma cells derive) are resistant to such noxious factors as ultraviolet light and reactive oxygen species. Targeted melanoma therapies are, so far, largely unsuccessful, and new ones, such as adjuvant inhibition of melanogenesis, are under development. NIH Public Access Keywordsbiotherapy; chemokine; integrin; melanoma; metastasis; sentinel lymph node Melanoma occurrence, staging & detectionBefore we review several concepts related to mechanisms of melanoma metastasis and treatment, we will briefly describe the currently available data about melanoma occurrence, the currently used system that divides melanoma patients into groups with different survival rates and the methods used to detect melanoma cells beyond the primary cutaneous tumor site. Since metastasis is the most important predictor of the patient's prognosis, there is a lot of effort directed at unequivocal determination of their presence in the adjacent epidermis, sentinel lymph nodes, circulation and distant sites (Box 1).Before melanoma cells metastasize they extend into the adjacent epidermis. 'Field cells' were characterized by Bastian et al. [3]. Epidermis adjacent to the acr...

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Section: Melanoma Occurrence Staging and Detectionmentioning

confidence: 99%

Current concepts of metastasis in melanoma

Zbytek

Carlson

Granese

et al. 2008

Expert Review of Dermatology

210

188

View full text Add to dashboard Cite

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“…The presence of circulating tumour cells is correlated with prognosis in breast, prostate and colorectal cancer patients [9-18]. CMCs can be detected by reverse transcription polymerase chain reaction (RT-PCR) and results have shown detection of melanoma markers correlates with poor prognosis [1,3,19-22]. Furthermore, RT-PCR has demonstrated expression of melanoma markers in peripheral blood of early stage patients with no clinical evidence of metastasis, suggesting CMCs are present in all disease stages [3,20,21].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a multi-marker immunomagnetic enrichment assay for the quantification of circulating melanoma cells

et al. 2012

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BackgroundCirculating melanoma cells (CMCs) are thought to be valuable in improving measures of prognosis in melanoma patients and may be a useful marker of residual disease to identify non-metastatic patients requiring adjuvant therapy. We investigated whether immunomagnetic enrichment targeting multiple markers allows more efficient enrichment of CMCs from patient peripheral blood than targeting a single marker. Furthermore, we aimed to determine whether the number of CMCs in patient blood was associated with disease stage.MethodsWe captured CMCs by targeting the melanoma associated markers MCSP and MCAM as well as the melanoma stem cell markers ABCB5 and CD271, both individually and in combination, by immunomagnetic enrichment. CMCs were enriched and quantified from the peripheral blood of 10 non-metastatic and 13 metastatic melanoma patients.ResultsTargeting all markers in combination resulted in the enrichment of more CMCs than when any individual marker was targeted (p < 0.001-0.028). Furthermore, when a combination of markers was targeted, a greater number of CMCs were enriched in metastatic patients compared with non-metastatic patients (p = 0.007).ConclusionsOur results demonstrated that a combination of markers should be targeted for optimal isolation of CMCs. In addition, there are significantly more CMCs in metastatic patients compared with non-metastatic patients and therefore quantification of CMCs may prove to be a useful marker of disease progression.

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“…In particular, molecular markers can be useful tools for the early detection of disseminated tumour cells in cancer patients [7,8], whereas PCR-based techniques have already been applied to the diagnosis of subclinical cancer diseases, spreading and monitoring of the treatment response [9]. Several molecular markers for the detection of disseminated tumor cells in the blood of melanoma patients have been investigated [10][11][12][13][14] and, among them, tyrosinase (a key enzyme involved in the biosynthesis of melanin expressed by melanocytes and melanoma cells) appears to be one of the most effective, as its transcripts are generally not detected in blood samples from healthy donors [15]. Tyrosinase has been investigated mainly on cutaneous melanoma, but some studies [16][17][18] have also evaluated tyrosinase mRNA levels in patients with uveal melanoma.…”

Section: Introductionmentioning

confidence: 99%

Tyrosinase mRNA levels in the blood of uveal melanoma patients: correlation with the number of circulating tumor cells and tumor progression

Pinzani¹,

Mazzini

Salvianti³

et al. 2010

Melanoma Research

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We measured tyrosinase mRNA levels by real-time quantitative reverse transcription-PCR (qRT-PCR), in the blood of patients with uveal melanoma. Results were correlated with clinical data and, in a subgroup of patients, with the number of circulating tumor cells (CTC) assessed using isolation by size of epithelial tumor cells (ISET). Forty-one patients with uveal melanoma were longitudinally investigated over a period of 5 years. The standard curve of the qRT-PCR method used melanoma cell line SK-MEL-28, added to the blood of normal donors and it was calibrated on a synthetic RNA standard (1 SK-MEL-28 cell corresponding to 18 tyrosinase mRNA copies) to improve the procedural standardization to facilitate the comparison of data collected at different laboratories. Increased tyrosinase mRNA levels were found in at least one of the blood samples in 20 of 41 (49%) uveal melanoma patients (median 0.8 SK-MEL-28 cell equivalents/ml blood; range 0.1-14.4). A significant correlation was found between mRNA tyrosinase levels and tumor dimension (P<0.01), disease-free and overall survival (P<0.05). CTC were isolated by ISET in five of 16 patients (5.8, 2.33, 2.00, 1.25, and 0.75 CTC/ml of blood) and the corresponding tyrosinase mRNA levels were 2.13, 1.37, 0.83, 0.58, and 0.35 SK-MEL-28 cell equivalents/ml of blood. Tyrosinase was undetectable in 11 ISET-negative patients. Tyrosinase assay by qRT-PCR is a noninvasive method for the detection of tumor progression in uveal melanoma patients. The mRNA tyrosinase levels can be taken as an indirect parameter correlated to the number of CTC isolated from blood by ISET.

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Early Detection of Melanoma Progression by Quantitative Real-time RT-PCR Analysis for Multiple Melanoma Markers

Cited by 15 publications

References 34 publications

Current concepts of metastasis in melanoma

Current concepts of metastasis in melanoma

Evaluation of a multi-marker immunomagnetic enrichment assay for the quantification of circulating melanoma cells

Tyrosinase mRNA levels in the blood of uveal melanoma patients: correlation with the number of circulating tumor cells and tumor progression

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