TYRO3, AXL, MER (TAM) Receptor Expression in Korean Cutaneous Melanoma

Melanoma accounts for most skin cancer deaths despite lower incidence rates in Asia compared to Western countries 1 .Nearly 90% of cutaneous melanomas harbor oncogenic mutations in genes such as BRAF and c-KIT 2 .The mutational landscape varies by ethnicity and tumor subtype.In Korean patients, BRAF mutations occur in approximately 15%-30%, predominantly in superficial spreading melanomas, while c-KIT mutations are enriched in acral lentiginous melanoma and mucosal melanoma (10%-25%) 3 .Although BRAF and MEK inhibitors have shown clinical success, challenges including short response durations and acquired resistance highlight the need for combination therapies 4 .The TYRO3, AXL, and MER (TAM) receptors, a family of receptor tyrosine kinases, have gained attention for their roles in various cancers 5 .In melanoma, AXL regulates cell invasion and motility, TYRO3 promotes tumor growth and regulates microphthalmia-associated transcription factor (MITF), while MER is associated with cell proliferation and correlates with disease progression 6,7 .However, data on TAM receptors in cutaneous melanoma, particularly among Asians, are sparse.This study aimed to examine TAM receptor expression in Korean cutaneous melanoma patients and explore clinicopathologic correlations.We retrospectively reviewed 45 melanoma cases from Ewha Womans University Mokdong Hospital, Seoul, Korea, between 2003 and 2013.The Institutional Review Board (IRB) approved this study (IRB No. 2020-07-030).Clinical and pathological data were thoroughly reviewed, including Breslow thickness, ulceration presence, and melanoma subtype classification.Melanoma subtypes were categorized according to morphology and histology into acral lentiginous melanoma (ALM), superficial spreading melanoma (SSM), and nodular melanoma (NM).For immunohistochemical analysis, formalin-fixed, paraffin-embedded sections underwent standard deparaffinization and antigen retrieval with sodium citrate solution.Primary antibodies for TYRO3 (ab176026), AXL (ab72069), and MER (ab52968, Abcam, UK) were applied, followed by biotinylated anti-rabbit secondary antibody and detection using 3-amino-9-ethylcarbazole chromogen with hematoxylin counterstaining.BRAF mutation status was determined using VE1 anti-BRAF V600E antibody 8 .Two dermatologists, blinded to patient data, independently evaluated TAM receptor expression in melanoma cells.Staining was semi-quantitatively scored for extent (0=0%, 1=1%-10%, 2=11%-50%, 3=51%-100%) and intensity (0=negative, 1=weak, 2=moderate, 3=strong), with composite immunoreactivity scores (0-6) calculated by summing both parameters 9 .Cases with scores 1 were considered positive.Statistical analysis was performed using SPSS 20.0 (IBM Corp., Armonk, NY, USA).