Schuster Ronny, Bechrakis Nikolaos E, Stroux Andrea, Busse Antonia, Schmittel Alexander, Scheibenbogen Carmen, Thiel Eckhard, Foerster Michael H, Keilholz Ulrich
Department of Medicine III (Hematology, Oncology, and Transfusion Medicine), Charité, Campus Benjamin Franklin, Berlin, Germany.
Clin Cancer Res. 2007 Feb 15;13(4):1171-8. doi: 10.1158/1078-0432.CCR-06-2329.
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.
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.
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.
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.
本研究旨在确定在高危原发性葡萄膜黑色素瘤患者中，通过定量逆转录聚合酶链反应（RT-PCR）检测循环肿瘤细胞是否具有预后相关性。
收集110例高危非转移性葡萄膜黑色素瘤患者在初次治疗或随访时的血样。通过实时RT-PCR分析酪氨酸酶和MelanA/MART1的mRNA表达，并通过单因素和多因素分析将其与就诊时及随访时的临床数据进行比较。
RT-PCR检测在110例患者中的11例呈阳性结果，其中酪氨酸酶阳性5例，MelanA/MART1阳性5例，1例样本两种标志物均为阳性。中位随访22个月时，25%的患者发生转移，15%的患者死亡。单因素统计分析显示，RT-PCR和最大肿瘤直径是转移发生和生存的重要预后因素。在Cox比例风险模型中，RT-PCR结果和最大肿瘤直径可预测转移（风险比分别为7.3和2.6），而PCR结果、最大肿瘤直径和卡诺夫斯基功能状态是疾病特异性生存的显著变量（风险比分别为22.6、4.7和6.0）。对单个RT-PCR结果的分析显示，酪氨酸酶和MelanA/MART1转录本均为独立的预后因素。
酪氨酸酶或MelanA/MART1转录本的存在是高危原发性葡萄膜黑色素瘤患者后续发生转移和生存的独立预后因素，可用于选择患者进行辅助治疗研究。
