PO.PS01.03 · 人群科学

多元化城市人群中肢端黑色素瘤独特的临床与分子特征——包括极低的脑转移发生率：来自纽约市布朗克斯队列的启示

Distinct clinical and molecular features of acral melanoma in a diverse urban population including very low incidence of brain metastasis: Insights from a Bronx cohort in NYC

编号 5083 展板 23 时间 4/21 09:00–12:00 区域 Section 36 主讲 Katherine Kovrizhkin

分会场 Etiology and Molecular Epidemiology Approaches to Decipher Cancer Disparities

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作者与单位 Authors & Affiliations

Katherine Kovrizhkin¹, Tianyun Jiang¹, Matan Uriel¹, Emily Nadelmann¹, Katia Papalezova¹, Beth N. McLellan², Jee-Young Moon¹, Yvonne Saenger¹

¹Albert Einstein College of Medicine, Bronx, NY,²Montefiore Einstein, Bronx, NY

摘要 Abstract

中文摘要

引言：肢端黑色素瘤（AM）是一种罕见的黑色素瘤亚型，对少数族裔人群造成不成比例的影响。与非肢端皮肤黑色素瘤（NACM）相比，AM具有独特的临床与分子特征。布朗克斯拥有医疗资源匮乏的多元化人群，且AM发病率相对较高，因此我们试图明确该人群中AM的关键特征。方法：我们在Montefiore医疗中心（MMC，纽约州布朗克斯）对1984—2024年诊断为黑色素瘤的患者进行了回顾性病历审查，共识别出550例患者；提取了临床、病理、治疗及结局数据。统计学比较对连续变量/等级变量采用Mann-Whitney U检验，对分类变量采用卡方检验，若任一数值小于10则采用Fisher精确检验。P值<0.05被视为具有统计学意义。未发表数据：与TCGA相比，MMC患者年龄更大（中位数68.0 vs. 58.0，p<0.001），且女性比例更高（45.0% vs. 38.3%，p=0.038）。西班牙裔（19.5% vs. 2.3%）与非裔美国人（8.3% vs. 0.2%）比例更高，AM病例所占比例也更大（17.0% vs. 0.4%）（均p<0.001）。在MMC，AM患者就诊时分期显著高于NACM患者（p=0.010）。相反，AM病例中脑转移发生率为0%，而NACM为22.2%（p=0.002）。在有数据可用的病例中，BRAF突变见于18.1%的AM病例，而NACM为34.1%。在随访>12个月且因III—IV期疾病接受免疫检查点阻断（ICB）治疗的患者中，AM患者对ICB的持久缓解率（>12个月）较低（11.1% vs. 33.3%）。持久缓解与总生存期密切相关（p=0.005）。AM患者与NACM患者的总生存期无差异。使用NanoString平台对Roswell、ECOG及MMC队列进行的RNA表达谱分析显示，与NACM相比，AM中CCL27（一种对T细胞募集至关重要的趋化因子）表达显著下调。组织分析显示，AM的髓过氧化物酶（MPO）中位比例显著更高（p=0.011），并呈现CD8/MPO比值降低的趋势（p=0.066），提示肿瘤微环境发生改变。结论：我们的数据集突显了AM在疾病表现、肿瘤生物学及结局方面的关键差异，强调了扩大国家数据库以纳入包括西班牙裔和非裔美国人在内的多元化人群的必要性，因为其进展模式可能不同于东亚或欧洲较为同质人群中的AM。就诊分期更晚，加之无脑转移及独特的肿瘤微环境，提示美国多元化AM人群需要量身定制的管理策略。

查看英文原文 English abstract

Introduction: Acral melanoma (AM) is a rare melanoma subtype that disproportionately affects minority populations. AM has distinct clinical and molecular features compared with non-acral cutaneous melanomas (NACM). The Bronx has an underserved diverse population anda relatively high incidence of AM and therefore we sought to define key features of AM in this population. Methods : A retrospective chart review was conducted at Montefiore Medical Center (MMC, Bronx, NY) of patients diagnosed with melanoma from 1984-2024, identifying 550 patients; clinical, pathologic, treatment, and outcome data were extracted. Statistical comparisons used the Mann-Whitney U test for continuous/ordinal variables and chi-square for categorical variables or Fisher's exact test if any value was less than 10. P-values <0.05 were considered statistically significant. Unpublished Data: Compared with TCGA, MMC patients were older (median 68.0 vs. 58.0, p<0.001) and more often female (45.0% vs. 38.3%, p=0.038). There was a higher proportion of Hispanics (19.5% vs. 2.3%) and African Americans (8.3% vs. 0.2%), as well as a greater percentage of AM cases (17.0% vs 0.4%) (all p<0.001). At MMC, patients with AM presented at significantly higher stages compared to those with NACM (p=0.010). Conversely, brain metastases developed in 0% of AM cases as compared with 22.2% (p=0.002) of NACM. BRAF mutations were found in 18.1% of AM cases versus 34.1% of NACM cases for whom data was available. Among patients with >12 months follow-up receiving immune checkpoint blockade (ICB) for stage III-IV disease, AM patients had a lower durable rate of response (>12 months) to ICB (11.1% vs 33.3%). Durable response correlated strongly with overall survival (p=0.005). No difference in overall survival was observed between patients diagnosed with AM and those with NACM. RNA expression profiling using the NanoString platform across Roswell, ECOG, and MMC cohorts demonstrated a statistically significant downregulation of CCL27, a chemokine critical for T-cell recruitment, in AM versus NACM. Tissue analysis revealed AMs had a significantly higher median myeloperoxidase (MPO) proportion (p=0.011) and a trend toward a reduced CD8/MPO ratio (p=0.066), suggesting altered tumor microenvironment. Conclusions: Our dataset highlights key differences in disease presentation, tumor biology, and outcomes of AM, underscoring the need to expand national databases for diverse populations including Hispanics and African Americans because patterns of progression may differ from AM in more homogeneous populations in East Asia or Europe. Presentation at more advanced stages coupled with the absence of brain metastases and a unique tumor micro-environment suggest a need for tailored management of diverse populations with AM in the US.

利益披露 Disclosure

K. Kovrizhkin, None.. T. Jiang, None.. M. Uriel, None.. E. Nadelmann, None.. K. Papalezova, None. Y. Saenger, NextPoint Therapeutics ). Regeneron advisory Board.

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