Division of Surgical Oncology, Yale University School of Medicine, New Haven, CT.
Division of Medical Oncology, Yale University School of Medicine, New Haven, CT.
JCO Precis Oncol. 2024 Apr;8:e2300702. doi: 10.1200/PO.23.00702.
Melanocortin-1 receptor (MC1R) plays a critical role in human pigmentation and DNA repair mechanisms. MC1R-targeting agents are being investigated in clinical trials in patients with melanoma, yet large studies investigating the rate and degree of MC1R expression in primary and metastatic human melanoma tissue are lacking.
Using tissue microarrays containing three large cohorts of 225 cases of benign nevi, 189 with primary melanoma, and 271 with metastatic melanoma, we applied quantitative immunofluorescence and immunohistochemistry to comprehensively study MC1R protein expression.
We show a stepwise elevation of MC1R expression in different stages of melanoma progression (nevi, primary, metastasis). Higher MC1R expression was seen in deeper (>1 mm) primary lesions and ulcerated lesions and was associated with shorter survival in primary and metastatic tumors. On multivariable analysis, Breslow thickness, male sex, and chronic sun exposure were independent predictors of worse overall survival in the primary melanoma cohort.
Our data suggest that MC1R might be a valuable drug target in aggressive melanoma. Additional studies are warranted to determine its functional significance in melanoma progression and its utility as a predictive biomarker in patients receiving MC1R-directed therapies.
黑素皮质素 1 受体（MC1R）在人类色素沉着和 DNA 修复机制中起着关键作用。目前正在临床试验中研究针对 MC1R 的药物，用于治疗黑色素瘤患者，但缺乏针对原发性和转移性人类黑色素瘤组织中 MC1R 表达率和程度的大型研究。
使用包含三个大队列的组织微阵列，包括 225 例良性痣、189 例原发性黑素瘤和 271 例转移性黑素瘤，我们应用定量免疫荧光和免疫组织化学技术全面研究了 MC1R 蛋白表达。
我们发现 MC1R 表达在黑色素瘤进展的不同阶段（痣、原发性、转移）逐渐升高。在较深（>1 毫米）的原发性病变和溃疡性病变中观察到更高的 MC1R 表达，与原发性和转移性肿瘤的生存率降低相关。多变量分析显示，Breslow 厚度、男性、慢性阳光暴露是原发性黑素瘤队列总生存较差的独立预测因素。
我们的数据表明，MC1R 可能是侵袭性黑色素瘤的一个有价值的药物靶点。需要进一步的研究来确定其在黑色素瘤进展中的功能意义及其作为接受 MC1R 靶向治疗患者的预测生物标志物的效用。
