Abstract 1358: Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma
Authors: Huang Rong , Shen Gaigai , Ren Yu , Zheng Kelin , Wang Jiayu , Shi Yan , Yin Jiani C. , Qin Lanqun , Zhang Guiying , Zhao Mengke , Su Xinyu , Li Luqiao , Wang Fufeng , Tang Haimeng , Shao Yang , Liu Baorui , Zou Zhengyun 
Published: April 2023

Abstract
Purpose: Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment (TIME) of AM patients to gain insights into disease prognosis and potential treatment strategies.
Methods: Tissue samples from 90 AM patients were subjected to next-generation sequencing (NGS) and multiplexed immunohistochemistry (mIHC) tests. The prognostic potential of various mutational features and immune cell compositions were analyzed.
Results: The majority of patients presented with stage II (45.6%) and stage III (38.9%) disease. The most common histological subtype was acral lentiginous melanoma (ALM, 44.4%), followed by nodular melanoma (NM, 33.3%) and superficial spreading melanoma (SSM, 11.1%). None of the patients had received anti-tumor treatment prior to surgery and 73.3% received treatments following surgery, including interferon, interferon combined with other drugs, chemotherapy, and anti-PD-1 therapy. The median disease-free survival (mDFS) was 21.3 months and median overall survival (mOS) was 60 months. More advanced stage and histological subtypes of NM and ALM were associated with worse prognosis in AM patients (HR=2.74, 95% CI=1.34-5.60, p = 0.01; HR=5.16, 95% CI=1.51-17.63, p = 0.01, respectively), while patients who received post-surgical treatments had better survival (HR=0.31, 95% CI=0.15-0.63, p&lt;0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications (HR=4.85, 95% Cl=1.72-13.70, p&lt;0.01) and PTPN11 mutations (HR=5.73, 95% Cl=1.44-22.80, p = 0.01) were associated with shorter OS in AM patients. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR=0.34, 95% CI=0.15-0.77, p = 0.01). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin ( p = 0.06), which likely explains the poor prognosis in such patients.
Conclusions: Our study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and TIME profiles in AM patients and identified candidate prognostic factors.
KeywordsAcral melanoma; tumor immune microenvironment; CDK4; M1 macrophages; prognostic factors
Citation Format: Rong Huang, Gaigai Shen, Yu Ren, Kelin Zheng, Jiayu Wang, Yan Shi, Jiani C. Yin, Lanqun Qin, Guiying Zhang, Mengke Zhao, Xinyu Su, Luqiao Li, Fufeng Wang, Haimeng Tang, Yang Shao, Baorui Liu, Zhengyun Zou. Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1358.