MITF expression in acral melanoma tissues and its association with clinical, pathological characteristics and prognosis

Tong WANG; Wei SUN; Yu XU; Tu HU; Wanlin LIU; Qiongdan ZHENG; Zijian ZOU; Zirui DONG; Wenjie MA; Yong CHEN

doi:10.19401/j.cnki.1007-3639.2025.09.006

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MITF expression in acral melanoma tissues and its association with clinical, pathological characteristics and prognosis

Article | 更新时间：2025-12-31

- MITF expression in acral melanoma tissues and its association with clinical, pathological characteristics and prognosis
- China Oncology Vol. 35, Issue 9, Pages: 859-866(2025)
- 作者机构：
  
  复旦大学附属肿瘤医院骨软组织外科，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
- 基金信息：
  
  General Program of the National Natural Science Foundation of China(82272857);General Program of the National Natural Science Foundation of China(82373385);Young Scientists Fund of the National Natural Science Foundation of China(82303608)
- DOI：10.19401/j.cnki.1007-3639.2025.09.006
  CLC： R739.5
- Received：21 May 2025，
  
  Revised：2025-07-15，
  
  Published：30 September 2025
- 稿件说明：
移动端阅览
Tong WANG, Wei SUN, Yu XU, et al. MITF expression in acral melanoma tissues and its association with clinical, pathological characteristics and prognosis[J]. China Oncology, 2025, 35(9): 859-866.
DOI：

Tong WANG, Wei SUN, Yu XU, et al. MITF expression in acral melanoma tissues and its association with clinical, pathological characteristics and prognosis[J]. China Oncology, 2025, 35(9): 859-866. DOI： 10.19401/j.cnki.1007-3639.2025.09.006.

摘要

背景与目的：

小眼畸形相关转录因子（microphthalmia-associated transcription factor，MITF）在黑色素瘤的发生、发展过程中发挥着复杂的多层次调控作用。已有大量关于MITF的研究在皮肤型黑色素瘤（cutaneous melanoma，CM）中进行，但MITF在肢端型黑色素瘤（acral melanoma，AM）中的研究却十分有限。本研究回顾性分析AM患者的MITF表达情况与临床、病理学特征及预后的相关性，为患者的预后评估和个体化治疗方案制订提供依据。

方法：

本研究纳入2008年3月—2022年2月在复旦大学附属肿瘤医院进行原发灶切除，术后病理学检查诊断为恶性黑色素瘤的患者，取得患者手术切除标本制成组织芯片（tissue microarray，TMA）。本研究获复旦大学附属肿瘤医院医学伦理委员会批准（伦理编号：2203-ZZK-69-3）。从复旦大学附属肿瘤医院电子数据库中查阅患者的基本信息、临床、病理学特征，整理出与组织芯片孔位逐一对应的患者信息总表。切取完整的组织芯片进行免疫组织化学（immunohistochemistry，IHC）染色，由3名病理科医师独立在显微镜下进行阅片，评估MITF的表达情况。依据MITF表达水平对患者进行分层，统计分析两组患者的临床、病理学特征及预后的差异。

结果：

共纳入137例AM患者。MITF表达水平与T分期、N分期、美国癌症联合会（American Joint Committee on Cancer，AJCC）分期、Clark分级、前哨淋巴结、溃疡有关。调整混杂因素后进行多因素分析，结果显示，N分期和溃疡是MITF高表达的独立危险因素。生存分析显示，MITF高表达或更高的T分期预示着更短的无病生存期（disease-free survival，DFS）。MITF高表达患者的总生存期（overall survival，OS）在术后观察或细胞因子治疗组与辅助免疫检查点抑制剂（immune checkpoint inhibitor，ICI）治疗组间并无显著差异，而MITF低表达的患者能够从辅助ICI治疗中显著获益。

结论：

较高的N分期或合并溃疡预示着AM患者的肿瘤细胞内MITF呈高表达，而高表达MITF是疾病早期出现复发、转移甚至死亡的危险信号。此外，MITF低表

达的患者可以从术后辅助ICI治疗中获益。MITF不仅可以辅助黑色素瘤的诊断，还能够为临床预后评估和个体化治疗方案的制订提供依据。

Abstract

Background and purpose:

The microphthalmia-associated transcription factor (MITF) plays a complex role in melanoma pathogenesis and progression. It is known to regulate multiple processes both in melanocytes and melanoma cells. While numerous studies have explored MITF in cutaneous melanoma (CM)

research in acral melanoma (AM) is still limited. This study retrospectively analyzed the correlation between MITF expression and clinical

pathological characteristics and prognosis in AM patients

providing a basis for prognosis evaluation and personalized treatment plan formulation for patients.

Methods:

Patients who underwent primary resection of AM at Fudan University Shanghai Cancer Center from March 2008 to February 2022 were included. All surgical samples were diagnosed by clinical histopathology and used to construct the tissue microarray (TMA). This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center (approval number: 2203-ZZK-69-3). Cutting complete tissue microarray and evaluating MITF expression levels by immunohistochemistry (IHC) staining were carried out. The results were independently assessed and scored by three pathologists. Clinical and pathological data were collected from the hospital’s electronic medical record system

and each patient’s data was matched to their corresponding tissue sample on the chip. Patients were stratified into two groups based on MITF expression levels. Statistical analyses were performed to assess differences in clinical

pathological characteristics and survival outcomes between these two groups.

Results:

A total of 137 AM patients were included. MITF expression was significantly associated with T stage

N stage

American Joint Committee on Cancer (AJCC) stage

clark level

sentinel lymph node status

and presence of ulceration. Among these

stage and ulceration were independent risk factors for high expression of MITF after adjusting for confounding factors. Survival analysis showed that AM patients with high MITF expression or higher T stage were associated with shorter disease-free survival (DFS). Patients with high MITF expression showed no significant difference in overall survival (OS) between observation or cytokine therapy and adjuvant immune checkpoint inhibitor (ICI) therapy

whereas those with low MITF expression derived significant survival benefits from ICI treatment.

Conclusion:

A higher N stage or the presence of ulceration indicates high MITF expression in tumor cells

with high MITF levels serving as a warning signal for early recurrence

metastasis

and even death. Patients with low MITF expression could receive improved OS with early adjuvant ICI therapy. MITF could not only serve as an auxiliary diagnostic marker for melanoma but also provide a basis for clinical prognosis assessment and the formulation of personalized treatment plans.

关键词

Keywords

references

CHEN Y A , TEER J K , EROGLU Z , et al. Translational pathology, genomics and the development of systemic therapies for acral melanoma [J ] . Semin Cancer Biol , 2020 , 61 : 149 - 157 . DOI: S1044-579X(19)30343-8 http://doi.org/S1044-579X(19)30343-8

CHI Z H , LI S M , SHENG X N , et al. Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: a study of 522 consecutive cases [J ] . BMC Cancer , 2011 , 11 ( 1 ): 85.

HARTMAN M L , CZYZ M . MITF in melanoma: mechanisms behind its expression and activity [J ] . Cell Mol Life Sci , 2015 , 72 ( 7 ): 1249 - 1260 . DOI: 10.1007/s00018-014-1791-0 http://doi.org/10.1007/s00018-014-1791-0

HEALTH CHINA N . National guidelines for diagnosis and treatment of melanoma 2022 in China (English version) [J ] . Chin J Cancer Res , 2022 , 34 ( 4 ): 335 - 342 .

邹孜瑊 , 孙伟 , 胡涂 , 等 . 前哨淋巴结活检在皮肤型和肢端型黑色素瘤临床诊疗中的价值 [J ] . 中国癌症杂志 , 2022 , 32 ( 12 ): 1168 - 1177 . DOI: 10.19401/j.cnki.1007-3639.2022.12.004 http://doi.org/10.19401/j.cnki.1007-3639.2022.12.004

ZOU Z J , SUN W , HU T , et al. Clinical value of sentinel lymph node biopsy in patients with cutaneous and acral melanoma [J ] . China Oncol , 2022 , 32 ( 12 ): 1168 - 1177 .

NEWELL F , WILMOTT J S , JOHANSSON P A , et al. Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity [J ] . Nat Commun , 2020 , 11 ( 1 ): 5259.

陈柳含 , 张洋洋 , 李先安 . 肢端恶性黑色素瘤临床特征及预后因素分析 [J ] . 中国癌症杂志 , 2019 , 29 ( 5 ): 362 - 371 . DOI: 10.19401/j.cnki.1007-3639.2019.05.006 http://doi.org/10.19401/j.cnki.1007-3639.2019.05.006

CHEN L H , ZHANG Y Y , LI X A . Analysis of clinical characteristics and prognostic factors of acral melanoma [J ] . China Oncol , 2019 , 29 ( 5 ): 362 - 371 .

KLEMEN N D , WANG M , RUBINSTEIN J C , et al. Survival after checkpoint inhibitors for metastatic acral, mucosal and uveal melanoma [J ] . J Immunother Cancer , 2020 , 8 ( 1 ): e000341.

CARVALHO L A D , AGUIAR F C , SMALLEY K S M , et al. Acral melanoma: new insights into the immune and genomic landscape [J ] . Neoplasia , 2023 , 46 : 100947 .

GARRAWAY L A , WIDLUND H R , RUBIN M A , et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma [J ] . Nature , 2005 , 436 ( 7047 ): 117 - 122 .

KUMAR S M , DAI J , LI S , et al. Human skin neural crest progenitor cells are susceptible to BRAF ( V600E )-induced transformation [J ] . Oncogene , 2014 , 33 ( 7 ): 832 - 841 .

RAMBOW F , MARINE J C , GODING C R . Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities [J ] . Genes Dev , 2019 , 33 ( 19/20 ): 1295 - 1318 .

GIULIANO S , CHELI Y , OHANNA M , et al. Microphthalmia-associated transcription factor controls the DNA damage response and a lineage-specific senescence program in melanomas [J ] . Cancer Res , 2010 , 70 ( 9 ): 3813 - 3822 . DOI: 10.1158/0008-5472.CAN-09-2913 http://doi.org/10.1158/0008-5472.CAN-09-2913

AUGUSTIN R C , NEWMAN S , LI A F , et al. Identification of tumor-intrinsic drivers of immune exclusion in acral melanoma [J ] . J Immunother Cancer , 2023 , 11 ( 10 ): e007567.

QUEK C , PRATAPA A , BAI X Y , et al. Single-cell spatial multiomics reveals tumor microenvironment vulnerabilities in cancer resistance to immunotherapy [J ] . Cell Rep , 2024 , 43 ( 7 ): 114392.

VIVAS-GARCÍA Y , FALLETTA P , LIEBING J , et al. Lineage-restricted regulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity [J ] . Mol Cell , 2020 , 77 ( 1 ): 120 - 137 .e9.

MALISSEN N , MACAGNO N , GRANJEAUD S , et al. HVEM has a broader expression than PD-L1 and constitutes a negative prognostic marker and potential treatment target for melanoma [J ] . Oncoimmunology , 2019 , 8 ( 12 ): e1665976.

LIU Z Z , CHEN K G , DAI J , et al. A unique hyperdynamic dimer interface permits small molecule perturbation of the melanoma oncoprotein MITF for melanoma therapy [J ] . Cell Res , 2023 , 33 ( 1 ): 55 - 70 . DOI: 10.1038/s41422-022-00744-5 http://doi.org/10.1038/s41422-022-00744-5

WEI C Y , SUN W , SHEN K J , et al. Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses [J ] . Nat Commun , 2023 , 14 ( 1 ): 8119.

LUKE J J , RUTKOWSKI P , QUEIROLO P , et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage ⅡB or ⅡC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial [J ] . Lancet , 2022 , 399 ( 10336 ): 1718 - 1729 .

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