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Molecular Staging in Stage II and III Melanoma Patients and Its Effect on Long-Term Survival

From the Department of Dermatology of the Charité, Humboldt University; Department of Medicine III, Campus Benjamin Franklin, Charité Berlin, Berlin; Department of Biometry and Medical Documentation and Department of Dermatology, University of Ulm, Ulm; Department of Dermatology, University of Mainz, Mainz, Germany; and Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Christiane Voit, MD, Universitätshautklinik Charité, Humboldt University, Schumannstr 20/21, 10117 Berlin, Germany; e-mail: christiane.voit{at}t-online.de

PURPOSE: To assess the prognostic value of serial reverse transcriptase polymerase chain reaction (RT-PCR) -based measurements of tyrosinase mRNA in peripheral blood of stage II and III melanoma patients.

PATIENTS AND METHODS: During routine follow-up of American Joint Committee on Cancer stage II and III melanoma patients, serial testing for tyrosinase transcripts in peripheral blood was performed by RT-PCR. The PCR results were compared with the clinical data collected during the follow-up.

RESULTS: Over a period of 3 years, 111 patients (78 stage II and 33 stage III patients) were enrolled, and tyrosinase determinations were carried out. The 6-year disease-specific survival probability was 97% for patients always showing negative RT-PCR results and 67% for patients who tested positive at least once. In a Cox proportional hazards model, the prognostic value of sex, age, site of primary tumor, histologic subtype, stage, Breslow's tumor thickness, Clark level, and the time-dependent variable PCR result was assessed. Patients with a positive RT-PCR test had a distinctly higher risk of dying from melanoma, with a hazard ratio of 12.6 (95% CI, 3.4 to 46.3; P < .001).

CONCLUSION: Our study shows a strong association between PCR and disease-specific survival time. Detection of tyrosinase mRNA in peripheral blood may be of similar importance for the clinical course of melanoma as the detection of micrometastatic disease in the sentinel lymph node. Whether a combination of these two factors leads to a better definition of the prognosis of melanoma patients is under investigation in current studies.

Supported by grant No. 70-2459-Ke2 from Deutsche Krebshilfe.

Both C.V. and M.K. contributed equally to this work.

Presented in part at the Oral Melanoma Session of the 38th Annual Meeting of the American Society of Clinical Oncology in Orlando, FL, May 18-21, 2002.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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