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Visualization of Circulating Melanoma Cells in Peripheral Blood of Patients with Primary Uveal Melanoma

Authors' Affiliations: ¹ Department of Dermatology and ² University Eye Hospital, Centre for Ophthalmology, Eberhard Karls University of Tuebingen, Tuebingen, Germany; and ³ Department of Ophthalmology, University of Lübeck, Lübeck, Germany, and ⁴ Institute for Biometry, University of Aachen, Aachen, Germany

Requests for reprints: Salvatore Grisanti, Department of Ophthalmology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck. Phone: 49-451-5002211; Fax: 49-451-5002671; E-mail: salvatore.grisanti{at}uk-sh.de or Anja Ulmer, Department of Dermatology, Universitäts Hautklinik, Eberhard Karls University of Tübingen, Liebermeisterstr. 25, 72076 Tuebingen, Germany. Phone: 49-7071-2984560; Fax: 49-7071-294580; E-mail: anja.ulmer{at}med.uni-tuebingen.de.

Purpose: In patients with uveal melanoma, tumor cell dissemination and subsequent formation of metastases are confined mainly to the hematogenous route. Here, we sought to isolate circulating melanoma cells in peripheral blood of patients with primary uveal melanoma and clinically localized disease.

Experimental Design: Blood samples from 52 patients with clinically localized uveal melanoma and from 20 control individuals were prospectively collected before therapy of the primary tumor. Tumor cells expressing the melanoma-associated chondroitin sulfate proteoglycan were enriched by immunomagnetic cell sorting and visualized by immunocytologic staining. Results were compared with clinical data at presentation.

Results: In 10 of 52 patients [19%; 95% confidence interval (95% CI), 10-33%], between 1 and 5 circulating melanoma cells were detected in 50 mL peripheral blood. No melanoma-associated chondroitin sulfate proteoglycan–positive cells were detected in any of the 20 controls examined. The presence of tumor cells in peripheral blood was associated with ciliary body invasion [odds ratio (OR), 20.0; 95% CI, 3.0-131.7], advanced local tumor stage (OR, 6.7; 95% CI, 1.8-25.4), and anterior tumor localization (OR, 4.0; 95% CI, 1.2-12.7), all established factors for uveal melanoma progression.

Conclusions: Immunomagnetic enrichment enables detection of intact melanoma cells in peripheral blood of patients with clinically localized ocular disease. Visualization and capturing of these cells provide a unique tool for characterizing potentially metastasizing tumor cells from a primary melanoma at an early stage of the disease.