Ehlers Justis P, Harbour J William
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Clin Cancer Res. 2005 Mar 1;11(5):1849-53. doi: 10.1158/1078-0432.CCR-04-2054.
Up to half of uveal melanoma patients die of metastatic disease. Treatment of the primary eye tumor does not improve survival in high-risk patients due to occult micrometastatic disease, which is present at the time of eye tumor diagnosis but is not detected and treated until months to years later. Here, we use microarray gene expression data to identify a new prognostic marker.
Microarray gene expression profiles were analyzed in 25 primary uveal melanomas. Tumors were ranked by support vector machine (SVM) and by cytologic severity. Nbs1 protein expression was assessed by quantitative immunohistochemistry in 49 primary uveal melanomas. Survival was assessed using Kaplan-Meier life-table analysis.
Expression of the Nijmegen breakage syndrome (NBS1) gene correlated strongly with SVM and cytologic tumor rankings (P < 0.0001). Further, immunohistochemistry expression of the Nbs1 protein correlated strongly with both SVM and cytologic rankings (P < 0.0001). The 6-year actuarial survival was 100% in patients with low immunohistochemistry expression of Nbs1 and 22% in those with high Nbs1 expression (P = 0.01).
NBS1 is a strong predictor of uveal melanoma survival and potentially could be used as a clinical marker for guiding clinical management.
多达一半的葡萄膜黑色素瘤患者死于转移性疾病。由于隐匿性微转移疾病的存在，对原发性眼肿瘤的治疗并不能提高高危患者的生存率，这种微转移疾病在眼肿瘤诊断时就已存在，但直到数月至数年之后才被检测和治疗。在此，我们使用微阵列基因表达数据来识别一种新的预后标志物。
对25例原发性葡萄膜黑色素瘤的微阵列基因表达谱进行分析。通过支持向量机（SVM）和细胞学严重程度对肿瘤进行排名。通过定量免疫组织化学对49例原发性葡萄膜黑色素瘤中的Nbs1蛋白表达进行评估。使用Kaplan-Meier生命表分析评估生存率。
尼美根断裂综合征（NBS1）基因的表达与SVM和细胞学肿瘤排名密切相关（P < 0.0001）。此外，Nbs1蛋白的免疫组织化学表达与SVM和细胞学排名均密切相关（P < 0.0001）。Nbs1免疫组织化学低表达患者的6年精算生存率为100%，而Nbs1高表达患者为22%（P = 0.01）。
NBS1是葡萄膜黑色素瘤生存的有力预测指标，有可能用作指导临床管理的临床标志物。
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