Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California.
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Clin Cancer Res. 2017 Nov 15;23(22):6888-6892. doi: 10.1158/1078-0432.CCR-17-1317. Epub 2017 Aug 8.
To validate the prognostic impact of combined expression levels of three markers (SPP1, RGS1, and NCOA3) in melanoma specimens from patients enrolled in the E1690 clinical trial of high-dose or low-dose IFNα-2b versus observation. Tissue was available from 248 patients. Marker expression was determined by digital imaging of immunohistochemically stained slides. The prognostic impact of each marker was first assessed by recording its expression value relative to the median. A multimarker index was then developed to combine marker expression levels by counting for each patient the number of markers with high expression. The impact of the multimarker index on relapse-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier analysis, and both univariate and multivariate Cox regression analyses. By Kaplan-Meier analysis, high multimarker expression scores were significantly predictive of RFS ( < 0.001) and OS ( < 0.001). Stepwise multivariate Cox regression analysis with backward elimination that included routine clinical and histologic prognostic factors revealed high multimarker expression scores and tumor thickness as the only factors significantly and independently predicting RFS and OS. Stepwise multivariate Cox regression analyses that also included treatment type and number of positive lymph nodes generated identical results for both RFS and OS. In the molecularly defined low-risk subgroup, patients treated with high-dose IFN had a significantly improved RFS compared with patients in the other two subgroups ( < 0.05). These results validate the independent impact of combined expression levels of SPP1, RGS1, and NCOA3 on survival of melanoma in a prospectively collected cohort. .
为了验证在 E1690 临床试验中纳入的高剂量或低剂量 IFNα-2b 与观察相比的黑素瘤患者标本中三种标志物（SPP1、RGS1 和 NCOA3）联合表达水平的预后影响。从 248 例患者中获得组织。通过免疫组织化学染色幻灯片的数字成像确定标志物表达。首先通过记录相对于中位数的表达值来评估每个标志物的预后影响。然后通过计数每位患者具有高表达的标志物数量来开发多标志物指数以结合标志物表达水平。通过 Kaplan-Meier 分析评估多标志物指数对无复发生存（RFS）和总生存（OS）的影响，并进行单变量和多变量 Cox 回归分析。通过 Kaplan-Meier 分析，高多标志物表达评分与 RFS（<0.001）和 OS（<0.001）显著相关。包括常规临床和组织学预后因素的逐步向后消除多变量 Cox 回归分析显示，高多标志物表达评分和肿瘤厚度是唯一显著且独立预测 RFS 和 OS 的因素。还包括治疗类型和阳性淋巴结数量的逐步多变量 Cox 回归分析对 RFS 和 OS 产生了相同的结果。在分子定义的低风险亚组中，与其他两个亚组相比，接受高剂量 IFN 治疗的患者的 RFS 显著改善（<0.05）。这些结果验证了 SPP1、RGS1 和 NCOA3 联合表达水平对前瞻性收集的队列中黑素瘤患者生存的独立影响。
