Article
Prognostic relevance of circulating tumor cells in metastatic uveal melanoma
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Published: | June 29, 2009 |
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Purpose: Uveal melanoma primarily metastasizes hematogenously with metastases often confined to the liver. The aim of this study was to investigate the presence of circulating tumor cells (CTC) in patients with metastatic disease as marker for systemic disease and to determine their prognostic relevance.
Experimental design: Blood samples from 68 patients with metastatic uveal melanoma, of whom 48 had visible metastases only in the liver, were collected at time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as surrogate marker for the presence of CTC was analysed by real-time RT-PCR and compared with patient characteristics, progression free and overall survival (PFS and OS).
Results: CTC were detected by PCR in 63% of all 68 patients and in 67% of the 48 patients with only liver metastases. Univariate analysis revealed PCR-result, serum lactate dehydrogenase (LDH) and location of metastases as prognostic factors for PFS. Prognostic factors for OS were PCR, LDH and Karnofsky performance status. Cox model analysis revealed PCR and LDH as independent prognostic factors for PFS (hazard ratios 2.2/3.5) and OS (hazard ratios 4.0/6.5). Combination of PCR and LDH divided the patient cohort into three groups with distinct prognosis.
Conclusions: CTC as evidence for systemic disease can be found in the majority of patients with metastatic uveal melanoma including patients with visible disease confined to the liver. Detection of CTC-specific mRNA transcripts for tyrosinase and MelanA/MART1 by PCR is a poor prognostic factor for PFS and OS. Characterisation of CTC could improve understanding of their biology.