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, N 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.

Key words: Acral melanoma, Tissue microarray, Microphthalmia-associated transcription factor, Clinical, pathological characteristics, Prognosis, Treatment