Circulating tumor cells as prognostic factor for distant metastases and survival in patients with primary uveal melanoma.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Schuster
Ronny
R
Department of Medicine III (Hematology, Oncology, and Transfusion Medicine), Charité, Campus Benjamin Franklin, Berlin, Germany.
Bechrakis
Nikolaos E
NE
Stroux
Andrea
A
Busse
Antonia
A
Schmittel
Alexander
A
Scheibenbogen
Carmen
C
Thiel
Eckhard
E
Foerster
Michael H
MH
Keilholz
Ulrich
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000097:blood / Q000235:genetics / Q000473:pathology*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014604:Uveal Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*
D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014442:Monophenol Monooxygenase