Detection of Circulating Melanoma Cells by a Two-marker Polymerase Chain Reaction Assay in Relation to Therapy

Bitisik, O; Çamlıca, Hakan; Duranyıldız, Derya; Taş, Faruk; Kurul, Sidika; Dalay, Nejat

doi:10.5483/bmbrep.2003.36.2.173

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…[7] A two-marker polymerase chain reaction (PCR) using melan-A and tyrosinase has been described for the detection of Circulating Malignant Cells (CMCs) in the peripheral blood of patients with skin melanoma. [8] The combination of these two markers was also described for the detection of CMCs in uveal melanoma. [9,10] However, only a few studies evaluated the co-expression of these immunohistochemical markers in primary uveal melanomas.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma

Fernandes¹,

Odashiro²,

Saraiva³

et al. 2007

J Carcinog

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BackgroundMelan-A and tyrosinase are new immunohistochemical markers that can be used in the diagnosis of melanocytic lesions. The aim of this study was to investigate the correlation between radiotherapy or clinicohistopathological parameters and the expression of melan-A and tyrosinase in uveal melanoma.MethodsThirty-six enucleated cases of uveal melanoma were studied. The formalin-fixed, paraffin-embedded specimens were immunostained with monoclonal antibodies against melan-A and tyrosinase. The samples were classified as either positive or negative. The chi-square or the Student-t tests were used to test for the correlation of the expression rates of melan-A and tyrosinase with clinico-pathological parameters.ResultsMelan-A and tyrosinase were positive in 33 (91.7%) and 35 (97.2%) of the specimens, respectively. There was no significant association between the expression of melan-A or tyrosinase and radiotherapy or any clinico-pathological parameter. All specimens were positive for at least one of the immunohistochemical markers.ConclusionTo the best of our knowledge this is the first study concluding that the expression of melanocytic markers such as melan-A and tyrosinase is not influenced by radiotherapy or any clinico-pathological parameter. Moreover, when tyrosinase and melan-A are used together, 100% of the formalin-fixed, paraffin-embedded uveal melanoma samples tested positive for one of those markers.

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Section: Introductionmentioning

confidence: 99%

Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma

Fernandes¹,

Odashiro²,

Saraiva³

et al. 2007

J Carcinog

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“…In this context, it is accepted that presence of CMCs is correlated with the clinical stage of patients and that detection of these cells in patients with early-stage disease may indicate a high risk of metastasis and a lower probability of overall survival [13]. Recent studies described tyrosinase RT-PCR results as a potentially useful molecular marker that may provide an early indication of therapy effectiveness [14]. However, other authors found no relationship between positive PCR for tyrosinase and disease-free or overall survival [15].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of RT‐PCR Tyrosinase Detection in Peripheral Blood of Melanoma Patients

et al. 2006

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Malignant melanoma (MM) prognosis has been related to tumour thickness and clinical stage and metastasis risk has been associated with presence of tumour cells in peripheral blood. The aim of this study was to determine the relationship between presence of tyrosinase in peripheral blood of MM patients and their clinical prognosis. Blood samples from 58 MM patients (stage I–IV) were analysed, using RT-PCR assay to detect tyrosinase mRNA. The results showed that positive RT-PCR assay for tyrosinase were significantly associated with clinical status and tumour thickness. After a median follow-up of 24 months, RT-PCR results were found to be significant correlated with recurrence (p < 0.05) and clinical stage III (p < 0.05). Separate analysis of stage III tumours to determine the prognostic value of tyrosinase presence in peripheral blood showed an overall 24-month survival rate of 70% in the RT-PCR negative group versus 10% in the positive group (p < 0.02). These results suggest that detection of circulating melanoma cells may be especially relevant in stage III patients, in whom RT-PCR positivity defines a subpopulation at high risk of recurrence.

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“…Therefore, MITF should also be analyzed in sequential multiple blood samples in further studies. It has also been shown that the detection of circulating melanoma cells in serial blood samples obtained before, during, and after treatment (immunotherapy, chemotherapy, or biochemotherapy) can be used to monitor patients' response to treatment [9,12,14,27,28,32]. Koyanagi et al [38] have shown that MITF detection decreased with adjuvant biochemotherapy treatment and that MITF detection after the treatment was associated with significantly lower survival.…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, several studies have shown that multiple-marker analysis allows for the detection of circulating melanoma cells in a higher percentage of melanoma patients than single-marker analysis [9][10][11][24][25][26][27][28]30,36]. Among the markers analyzed in these studies, some have shown high specificity for melanoma cells (MART-1, TRP-1, TRP-2, MAGE-3, paired box homeotic gene transcription factor 3, b1-4-N-acetylgalactosaminyltransferase), whereas others were found to be positive also in healthy volunteer samples (p97, MUC18, gp100) [9][10][11][24][25][26][27]30,36]. Our study has confirmed the advantage of multi-marker analysis for the detection of circulating melanoma cells that had been shown in earlier studies.…”

Section: Discussionmentioning

confidence: 99%

“…In 23 different studies analyzed by Tsao et al [6], 45% of melanoma patients with distant metastases were positive for tyrosinase on average. It has been shown that multiple-marker analysis enables detection of circulating melanoma cells in a higher percentage of melanoma patients than single-marker (usually tyrosinase) analysis [9][10][11][24][25][26][27][28]30,36].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of microphthalmia-associated transcription factor and tyrosinase as markers for circulating tumor cells detection in patients with melanoma

et al. 2010

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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 healthy volunteers were negative for both MITF and tyrosinase. Out of 201 blood samples from melanoma patients 32 were positive for MITF, 20 for tyrosinase, and four for both MITF and tyrosinase. Analysis of MITF as an additional marker to tyrosinase allowed for detection of circulating melanoma cells in a larger number of melanoma patients in comparison to tyrosinase analysis alone (48 vs. 20 positive). A positive value of MITF was associated with shorter progression-free (P=0.005) and overall survival (P=0.042). A positive value of tyrosinase was associated with shorter overall survival (P=0.012), whereas there was no significant association between the value of tyrosinase and progression-free survival. The value of MITF was selected with multivariate analysis as the independent prognostic factor for progression-free survival, whereas the only independent prognostic factor for overall survival was the stage of disease. This study has shown that MITF is a specific marker for detection of circulating melanoma cells that has a prognostic value in melanoma patients. Determination of MITF in addition to tyrosinase improved the detection of circulating melanoma cells in melanoma patients.

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Detection of Circulating Melanoma Cells by a Two-marker Polymerase Chain Reaction Assay in Relation to Therapy

Cited by 5 publications

References 29 publications

Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma

Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma

Prognostic Value of RT‐PCR Tyrosinase Detection in Peripheral Blood of Melanoma Patients

Prognostic value of microphthalmia-associated transcription factor and tyrosinase as markers for circulating tumor cells detection in patients with melanoma

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