Ulmer Anja, Beutel Julia, Süsskind Daniela, Hilgers Ralf-Dieter, Ziemssen Focke, Lüke Matthias, Röcken Martin, Rohrbach Martin, Fierlbeck Gerhard, Bartz-Schmidt Karl-Ulrich, Grisanti Salvatore
Department of Dermatology and University Eye Hospital, Centre for Ophthalmology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
Clin Cancer Res. 2008 Jul 15;14(14):4469-74. doi: 10.1158/1078-0432.CCR-08-0012.
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.
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.
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.
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.
在葡萄膜黑色素瘤患者中，肿瘤细胞的播散及随后转移灶的形成主要局限于血行途径。在此，我们试图从原发性葡萄膜黑色素瘤且临床疾病局限的患者外周血中分离循环黑色素瘤细胞。
前瞻性收集52例临床疾病局限的葡萄膜黑色素瘤患者及20例对照个体在原发性肿瘤治疗前的血样。通过免疫磁珠细胞分选富集表达黑色素瘤相关硫酸软骨素蛋白聚糖的肿瘤细胞，并通过免疫细胞化学染色进行可视化。将结果与就诊时的临床数据进行比较。
在52例患者中的10例（19%；95%置信区间[95%CI]，10 - 33%），在50 mL外周血中检测到1至5个循环黑色素瘤细胞。在所检测的20例对照中均未检测到黑色素瘤相关硫酸软骨素蛋白聚糖阳性细胞。外周血中存在肿瘤细胞与睫状体侵犯（优势比[OR]，20.0；95%CI，3.0 - 131.7）、局部肿瘤晚期（OR，6.7；95%CI，1.8 - 25.4）及肿瘤前部定位（OR，4.0；95%CI，1.2 - 12.7）相关，这些均是葡萄膜黑色素瘤进展的既定因素。
免疫磁珠富集能够检测临床疾病局限的眼部疾病患者外周血中的完整黑色素瘤细胞。对这些细胞的可视化和捕获为在疾病早期阶段表征原发性黑色素瘤中潜在转移的肿瘤细胞提供了一种独特的工具。
