Maher Nigel G, Vergara Ismael A, Long Georgina V, Scolyer Richard A
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Pathology. 2024 Mar;56(2):259-273. doi: 10.1016/j.pathol.2023.11.004. Epub 2023 Dec 20.
Biomarkers help to inform the clinical management of patients with melanoma. For patients with clinically localised primary melanoma, biomarkers can help to predict post-surgical outcome (including via the use of risk prediction tools), better select patients for sentinel lymph node biopsy, and tailor catch-all follow-up protocols to the individual. Systemic drug treatments, including immune checkpoint inhibitor (ICI) therapies and BRAF-targeted therapies, have radically improved the prognosis of metastatic (stage III and IV) cutaneous melanoma patients, and also shown benefit in the earlier setting of stage IIB/C primary melanoma. Unfortunately, a response is far from guaranteed. Here, we review clinically relevant, established, and emerging, prognostic, and predictive pathological biomarkers that refine clinical decision-making in primary and metastatic melanoma patients. Gene expression profile assays and nomograms are emerging tools for prognostication and sentinel lymph node risk prediction in primary melanoma patients. Biomarkers incorporated into clinical practice guidelines include BRAF V600 mutations for the use of targeted therapies in metastatic cutaneous melanoma, and the HLA-A∗02:01 allele for the use of a bispecific fusion protein in metastatic uveal melanoma. Several predictive biomarkers have been proposed for ICI therapies but have not been incorporated into Australian clinical practice guidelines. Further research, validation, and assessment of clinical utility is required before more prognostic and predictive biomarkers are fluidly integrated into routine care.
生物标志物有助于指导黑色素瘤患者的临床管理。对于临床局限性原发性黑色素瘤患者，生物标志物有助于预测术后结果（包括通过使用风险预测工具），更好地选择患者进行前哨淋巴结活检，并根据个体情况制定全面的随访方案。全身药物治疗，包括免疫检查点抑制剂（ICI）疗法和BRAF靶向疗法，已显著改善了转移性（III期和IV期）皮肤黑色素瘤患者的预后，并且在IIB/C期原发性黑色素瘤的早期治疗中也显示出益处。不幸的是，疗效远非有保证。在此，我们综述了临床相关的、已确立的和新兴的预后及预测性病理生物标志物，这些标志物可优化原发性和转移性黑色素瘤患者的临床决策。基因表达谱分析和列线图是原发性黑色素瘤患者预后评估和前哨淋巴结风险预测的新兴工具。纳入临床实践指南的生物标志物包括用于转移性皮肤黑色素瘤靶向治疗的BRAF V600突变，以及用于转移性葡萄膜黑色素瘤双特异性融合蛋白治疗的HLA-A∗02:01等位基因。已经提出了几种针对ICI疗法的预测性生物标志物，但尚未纳入澳大利亚临床实践指南。在更多的预后和预测性生物标志物顺利融入常规治疗之前，还需要进一步的研究、验证和临床效用评估。
