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Microphthalmia Transcription Factor as a Molecular Marker for Circulating Tumor Cell Detection in Blood of Melanoma Patients

Authors' Affiliations: ¹ Department of Molecular Oncology, John Wayne Cancer Institute at Saint John's Health Center; ² The Angeles Clinic and Research Institute, Santa Monica, California; ³ University of Colorado Cancer Center, Aurora, Colorado; ⁴ North Memorial Health Care, Hubert H. Humphrey Cancer Center, Robbinsdale, Minnesota; and ⁵ Department of Biostatistics, University of California at Los Angeles School of Medicine, Los Angeles, California

Requests for reprints: Dave S.B. Hoon, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404. Phone: 310-449-5267; Fax: 310-449-5282; E-mail: hoon{at}jwci.org.

Purpose: Microphthalmia transcription factor (Mitf), which is important in melanocyte development and melanoma growth, was assessed using real-time quantitative reverse transcription-PCR assay to investigate its expression as a marker for circulating melanoma cells in blood and determine the correlation with disease stage and survival in melanoma patients.

Experimental Design: In optimization studies for Mitf, we tested 15 melanoma cell lines, 41 peripheral blood lymphocytes from healthy volunteers, and 21 metastatic melanoma tissues. Blood specimens were procured from 90 patients with stage I (n = 20), stage II (n = 20), stage III (n = 28), and stage IV (n = 22) melanoma. Blood specimens were also obtained at four bleed intervals from 58 patients enrolled in a prospective multicenter trial of biochemotherapy before and after surgical treatment of American Joint Committee on Cancer stage III melanoma.

Results: Under the optimized conditions, Mitf was negative in healthy peripheral blood lymphocytes and positive in all melanoma cell lines and 18 (86%) melanoma tissues. In the 90 patients, the rate of Mitf detection was higher with increasing American Joint Committee on Cancer stage (P < 0.0001). In the 58 patients treated with biochemotherapy and surgery, Mitf detection decreased with treatment (P = 0.019). Mitf detection after treatment was associated with a significantly lower relapse-free (P < 0.0001) and overall (P = 0.001) survival and was a significant independent prognostic factor for relapse-free (risk ratio, 5.63; P = 0.0004) and overall (risk ratio, 5.36; P = 0.005) survival.

Conclusions: Mitf detection in blood can indicate subclinical metastatic disease and predict treatment outcome in melanoma patients.

Commentary

Microphthalmic-Associated Transcription Factor Integrates Melanocyte Biology and Melanoma Progression

Colin Goding and Frank L. Meyskens, Jr.
Clin. Cancer Res. 2006 12: 1069-1073. [Full Text] [PDF]

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