title: Prognostic relevance of circulating tumor cells in metastatic uveal melanoma.
abstract: OBJECTIVE
  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 a marker for systemic disease and to determine their prognostic relevance.
  
  
  METHODS
  Blood samples from 68 patients were collected at the time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as a surrogate marker for the presence of CTC was analyzed by real-time RT-PCR and compared with patient characteristics.
  
  
  RESULTS
  CTC were detected in 63% of all patients and in 67% of the 48 patients with only liver metastases. Univariate and multivariate analyses revealed PCR results and serum lactate dehydrogenase as independent prognostic factors for progression-free (hazard ratios 2.2/3.5) and overall survival (hazard ratios 4.0/6.5). Combination of PCR and lactate dehydrogenase divided the patient cohort into 3 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 progression-free and overall survival. Characterization of CTC could improve the understanding of their biology.
authors.affiliation: Department of Hematology and Oncology, Charité CBF, Berlin, Germany. ronny.schuster@charite.de
authors.forename: R
authors.initials: R
authors.lastname: Schuster
authors.forename: N E
authors.initials: NE
authors.lastname: Bechrakis
authors.forename: A
authors.initials: A
authors.lastname: Stroux
authors.forename: A
authors.initials: A
authors.lastname: Busse
authors.forename: A
authors.initials: A
authors.lastname: Schmittel
authors.forename: E
authors.initials: E
authors.lastname: Thiel
authors.forename: M H
authors.initials: MH
authors.lastname: Foerster
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008113:Liver Neoplasms / Q000556:secondary*; D058965:MART-1 Antigen / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000473:pathology / Q000556:secondary*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000097:blood* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D058965:MART-1 Antigen; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase; D014442:Monophenol Monooxygenase