Rothberg Bonnie E Gould, Rimm David L
Department of Internal Medicine, Yale Cancer Center, New Haven, CT, USA.
Methods Mol Biol. 2014;1102:227-58. doi: 10.1007/978-1-62703-727-3_13.
The outcome of Stage II melanoma is uncertain. Despite that 10-year melanoma-specific survival can approach 50 % following curative-intent wide local excision and negative sentinel lymph node biopsy, the adverse risk-benefit ratio of interferon-based adjuvant regimens precludes their use in most patients. The discovery and translation of protein-based prognostic biomarkers into the clinic offers the promise for residual risk stratification of Stage II melanoma patients beyond conventional clinicopathologic criteria to identify an additional subset of patients who, based upon tumor molecular profiles, might also derive benefit from adjuvant regimens. Despite incorporation of Ki-67 assays into clinical practice, systematic review of REMARK-compliant, immunostain-based prognostic biomarker assays in melanoma suggests that residual risk of recurrence might be best explained by a composite score derived from a small panel of proteins representing independent features of melanoma biology. Reflecting this trend, to date, five such multiparameter melanoma prognostic models have been published. Here, we review these five models and provide detailed protocols for discovering and validating multiparameter models including: appropriate cohort recruitment strategies, comprehensive laboratory protocols supporting fully quantitative chromogenic or fluorescent immunostaining platforms, statistical approaches to create composite prognostic indices recommended steps for model validation in independent cohorts.
II期黑色素瘤的预后尚不确定。尽管在进行根治性广泛局部切除且前哨淋巴结活检为阴性后，10年黑色素瘤特异性生存率可接近50%，但基于干扰素的辅助治疗方案的不良风险效益比使其无法应用于大多数患者。基于蛋白质的预后生物标志物的发现和临床转化为II期黑色素瘤患者的残余风险分层提供了希望，超越了传统的临床病理标准，以识别另外一部分患者，这些患者基于肿瘤分子特征，可能也能从辅助治疗方案中获益。尽管Ki-67检测已纳入临床实践，但对符合REMARK标准的黑色素瘤免疫染色预后生物标志物检测的系统评价表明，复发的残余风险可能最好由一个综合评分来解释，该评分来自一小部分代表黑色素瘤生物学独立特征的蛋白质。反映这一趋势的是，迄今为止，已发表了五个这样的多参数黑色素瘤预后模型。在此，我们回顾这五个模型，并提供发现和验证多参数模型的详细方案，包括：合适的队列招募策略、支持完全定量显色或荧光免疫染色平台的综合实验室方案、创建综合预后指数的统计方法、在独立队列中进行模型验证的推荐步骤。
