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Circulating Tumor Cells as Prognostic Factor for Distant Metastases and Survival in Patients with Primary Uveal Melanoma

Authors' Affiliations: Departments of ¹ Medicine III (Hematology, Oncology, and Transfusion Medicine) and ² Ophthalmology, and ³ Institute of Medical Informatics, Biometry, and Clinical Epidemiology, Charité, Campus Benjamin Franklin, Berlin, Germany

Requests for reprints: Ulrich Keilholz, Department of Medicine III, Charité-Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. Phone: 49-30-8445-3906; Fax: 49-30-8445-4021; E-mail: ulrich.keilholz{at}charite.de.

Purpose: The aim of this study was to determine in patients with high-risk primary uveal melanoma whether the detection of circulating tumor cells by quantitative reverse transcription-PCR (RT-PCR) is of prognostic relevance.

Experimental Design: Blood samples from 110 patients with high-risk nonmetastatic uveal melanoma were collected on the occasion of primary treatment or follow-up visit. mRNA expression of tyrosinase and MelanA/MART1 were analyzed by real-time RT-PCR and compared with clinical data at presentation and follow-up by univariate and multivariate analyses.

Results: The RT-PCR assay yielded a positive result in 11 of 110 patients, with five positive findings for tyrosinase and five for MelanA/MART1, and one sample positive for both markers. At a median follow-up of 22 months, 25% of patients had developed metastases and 15% had died. Univariate statistical analysis revealed RT-PCR and the largest tumor diameter as important prognostic factors for the development of metastases and for survival. In a Cox proportional hazard model, RT-PCR result and largest tumor diameter predicted metastases (hazard ratios 7.3 and 2.6, respectively), whereas PCR result, largest tumor diameter, and Karnofsky performance status were significant variables for disease-specific survival (hazard ratios 22.6, 4.7, and 6.0, respectively). Analysis of individual RT-PCR results revealed both tyrosinase and MelanA/MART1 transcripts as independent prognostic factors.

Conclusion: The presence of tyrosinase or MelanA/MART1 transcripts is an independent prognostic factor in patients with high-risk primary uveal melanoma for subsequent development of metastases and for survival and can be used to select patients for adjuvant treatment studies.

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