Molecular Tumor Markers in the Blood: Early Prediction of Disease Outcome in Melanoma Patients Treated With a Melanoma Vaccine

Wascher, Robert A.; Morton, Donald L.; Kuo, Calvin; Elashoff, Robert M.; Wang, He-Jing; Gerami, Mehri; Hoon, Dave S.B.

doi:10.1200/jco.2003.06.110

Cited by 47 publications

(37 citation statements)

References 16 publications

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“…In this study, predictive markers for clinical stage II patients were validated through molecular upstaging of SLNs (11,19 ). Previously, we have shown the significance of circulating melanoma cells in prediction of disease outcome in patients with stage III/IV melanoma (5,6 ). In the present study, we quantitatively demonstrated the differences in blood from patients with AJCC stages I/II and III/IV disease.…”

Section: Discussionsupporting

confidence: 50%

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Multimarker Quantitative Real-Time PCR Detection of Circulating Melanoma Cells in Peripheral Blood: Relation to Disease Stage in Melanoma Patients

et al. 2005

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Background: Detection of melanoma cells in circulation may be important in assessing tumor progression. The objective of this study was to develop a specific, reliable multimarker quantitative real-time reverse transcription-PCR (qRT) assay for detecting melanoma cells in patients' blood. Methods: We developed qRT assays for the mRNA of four melanoma-associated markers: MART-1, GalNAc-T, PAX-3, and MAGE-A3. In optimization studies, we tested 17 melanoma cell lines and 49 peripheral blood leukocyte (PBL) samples from volunteers. We performed RNA and melanoma cell dilution studies to assess the detection limits and imprecision of the assays. We measured the mRNAs in blood specimens from 94 melanoma patients [American Joint Committee on Cancer (AJCC) stage I, n ‫؍‬ 20; II, n ‫؍‬ 20; III, n ‫؍‬ 32; IV, n ‫؍‬ 22]. Results: All markers were frequently detected in melanoma cell lines, whereas none of the markers was detected in PBLs from volunteers. The qRT assay could detect 1 melanoma cell in 10 7 PBLs in the melanoma cell-dilution studies. Markers were detected in 15%, 30%, 75%, and 86% of melanoma patients with AJCC stage I, II, III, and IV disease, respectively. The number of positive markers and AJCC stage were significantly

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Section: Discussionsupporting

confidence: 50%

“…Although tumor cells may express all markers assessed, the concentrations of expressed marker mRNAs can vary. Because of the detection limits for mRNAs, this difference must be considered in developing sensitive and reliable qRT assays (5,6,17,18 ).…”

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Multimarker Quantitative Real-Time PCR Detection of Circulating Melanoma Cells in Peripheral Blood: Relation to Disease Stage in Melanoma Patients

et al. 2005

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“…However, CTC detection rates were remarkably similar across TNM stages (range 32-47.4%) and significantly different from those one would expect based on the survival rates observed in patients with different stages of disease ( Fig. 3; (29,36,45,53,57,58,64), the authors analyzed both OS and PFS.…”

Section: Ctc Prognostic Valuementioning

confidence: 99%

The Prognostic Value of Circulating Tumor Cells in Patients with Melanoma: A Systematic Review and Meta-analysis

Mocellin

Hoon

Ambrosi

et al. 2006

Clinical Cancer Research

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Background: The detection of circulating tumor cells (CTC) in patients with melanoma represents an appealing prognostic tool, but no consensus exists on this topic. We aimed to comprehensively and quantitatively summarize the evidence for the use of CTC to predict patients'clinical outcome. Methods: Fifty-three studies enrolling 5,433 patients were reviewed. Correlation of CTC status with tumor-node-metastasis disease stage and patients'overall (OS) and progression-free (PFS) survival was assessed by means of association statistics and meta-analysis, respectively. Results: CTC status correlated with both tumor-node-metastasis stage (stage I, 32%; stage II, 41.7%; stage III, 41.1%; stage IV, 47.4%; P trend < 0.0001) and survival (OS: hazard ratio, 2.42; 95% confidence interval, 1.7-3.45, P < 0.0001; PFS: hazard ratio, 2.45; 95% confidence interval, 1.78-3.38; P < 0.0001). However, statistical heterogeneity was significant for both OS and PFS, likely underscoring the wide variability in study design. Furthermore, CTC positivity rates in early stages were higher and in the metastatic setting were lower than expected, which indicates an unsatisfactory accuracy of currently available CTC detection assays. Conclusions: Our findings suggest that CTC might have a clinically valuable prognostic power in patients with melanoma. However, the heterogeneity of the studies thus far published warrants caution not to overestimate the favorable results of pooled data.

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“…Investigators have shown the clinical utility of circulating tumor cells (CTC) in blood as surrogate markers for subclinical disease and prognostic factors of disease outcome and treatment response (7)(8)(9)(10). CTC in blood are detected by quantitative real-time reverse transcription-PCR (RT-PCR) assay, which allows rapid and reproducible identification of a few tumor cells among millions of peripheral blood leukocytes (PBL; ref.…”

Section: Introductionmentioning

confidence: 99%

Association of Circulating Tumor Cells with Serum Tumor-Related Methylated DNA in Peripheral Blood of Melanoma Patients

et al. 2006

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Although previous studies have separately shown the utility of circulating tumor cells (CTC) or cell-free tumor-related DNA in blood of cancer patients, there has been no investigation of their association and/or the prognostic value of combining these assessments. To date, the true source of tumor-related DNA in serum remains unknown. We hypothesized that CTC is a possible origin of serum tumor-related methylated DNA and their combination can predict disease outcome. To test this hypothesis, we obtained matched pairs of peripheral blood lymphocytes and serum specimens simultaneously from 50 American Joint Committee on Cancer stage IV melanoma patients before administration of biochemotherapy. Peripheral blood leukocytes were analyzed for three mRNA markers of CTC: MART-1, GalNAc-T, and MAGE-A3. Sera were analyzed for two methylated DNA markers: RASSF1A and RAR-b2. CTC were detected in 13 of 15 (86%) patients with serum tumorrelated methylated DNA and only in 13 of 35 (37%) patients without methylated DNA (P = 0.001). The number of CTC markers detected significantly correlated with methylated DNA (P = 0.008). CTC and methylated DNA were significantly correlated with biochemotherapy-treated patients' outcome. Patients with both CTC and methylated DNA showed significantly poorer response to biochemotherapy (P = 0.02) and worse time to progression and overall survival (P = 0.009 and 0.02, respectively). The correlation between CTC and serum tumor-related methylated DNA and the significant effect of this correlation on disease outcome indicate that a composite molecular assessment in blood may be a useful determinant of disease status and efficacy of systemic therapy for melanoma. (Cancer Res 2006; 66(12): 6111-7)

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Molecular Tumor Markers in the Blood: Early Prediction of Disease Outcome in Melanoma Patients Treated With a Melanoma Vaccine

Cited by 47 publications

References 16 publications

Multimarker Quantitative Real-Time PCR Detection of Circulating Melanoma Cells in Peripheral Blood: Relation to Disease Stage in Melanoma Patients

Multimarker Quantitative Real-Time PCR Detection of Circulating Melanoma Cells in Peripheral Blood: Relation to Disease Stage in Melanoma Patients

The Prognostic Value of Circulating Tumor Cells in Patients with Melanoma: A Systematic Review and Meta-analysis

Association of Circulating Tumor Cells with Serum Tumor-Related Methylated DNA in Peripheral Blood of Melanoma Patients

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