Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma
Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma
复制标题
DOI：
10.1200/jco.2014.60.7002
复制
发表时间：
2015-08-10
影响因子：
45.3
通讯作者：
Suman, Vera J.
中科院分区：
文献类型：
--
作者：
Meves, Alexander;Nikolova, Ekaterina;Suman, Vera J.
根据美国临床肿瘤学会/外科肿瘤学会的建议，接受前哨淋巴结(SLN)活检的黑色素瘤患者中，不到20%的SLN阳性。通过对73例良性黑色素瘤、76例原发皮肤黑色素瘤和11例转移性黑色素瘤的研究，通过下一代测序发现了在黑色素瘤转移中起功能作用的基因簇，并通过定量聚合酶链式反应进行了验证。然后，我们使用聚合酶链式反应对360个连续的薄型和中厚型黑色素瘤的模型发展队列和146个黑色素瘤的验证队列中的基因表达进行了量化。令人感兴趣的结果是黑色素瘤诊断后90天内SLN活检转移。结果ITGB3、Lamb1、Plat和TP53的表达与SLN转移有关。包括这些分子变量和临床病理变量(患者年龄、布雷斯洛深度和肿瘤溃疡)的模型的预测能力显著高于仅考虑临床病理变量的模型，并且在验证队列中表现良好(曲线下面积为0.93；95%可信区间为0.87至0.97；假阳性率和假阴性率分别为22%和0%，以预测SLN转移风险为10%)。结论在黑色素瘤诊断的90天内，将细胞黏附相关基因表达变量添加到临床病理变量中可以提高对SLN转移患者的识别能力。(C)2015年度美国临床肿瘤学会
PurposeLess than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma.Patients and MethodsGene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables.ResultsITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk).ConclusionThe addition of cell adhesion-linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis. (C) 2015 by American Society of Clinical Oncology