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RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A
Lorenzo Nicolè1,2, Filippo Cappello1,3, Rocco Cappellesso3
1Department of Medicine (DIMED), University of Padova, Padova, Italy.
Abstract:
Malignant melanoma (MM) is the most lethal skin cancer. AXL is a tyrosine kinase receptor involved in several oncogenic processes and might play a role in blocking necroptosis (a regulated cell death mechanism) in MM through the downregulation of the necroptotic-related driver RIPK3. The aim of this study was to evaluate the clinical impact of the expression of AXL and RIPK3 in 108 primary cutaneous MMs. Association between AXL and RIPK3 immunoreactivity and clinical-pathological variables, sentinel lymph node status, and tumor-infiltrating lymphocytes (TILs) was assessed. Immunoreaction in tumor cells was detected in 30 cases (28%; range, 5%-80%) and in 17 cases (16%; range, 5%-50%) for AXL and RIPK3, respectively. Metastases in the sentinel lymph nodes were detected in 14 out of 61 patients, and these were associated with AXL-positive immunoreactivity in the primary tumor (p < 0.0001). No association between AXL and TILs was found. RIPK3 immunoreactivity was not associated with any variables. A final logistic regression analysis showed Breslow and AXL-positive immunoreactivity as the stronger predictor for positive sentinel node status [area under the receiver operating characteristic curve (AUC) of 0.96]. AXL could be a potential new biomarker for MM risk assessment, and it deserves to be further investigated in larger studies.
Insights
AXL receptor expression in primary malignant melanoma (MM) predicts sentinel lymph node metastasis. High AXL levels indicate increased risk, suggesting AXL as a potential biomarker for MM progression and patient stratification.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- Malignant melanoma (MM) is an aggressive skin cancer.
- AXL receptor tyrosine kinase is implicated in oncogenesis.
- AXL may inhibit necroptosis in MM by downregulating RIPK3.
Purpose of the Study:
- To investigate the clinical significance of AXL and RIPK3 expression in primary cutaneous MM.
- To correlate AXL and RIPK3 immunoreactivity with clinicopathological features and sentinel lymph node (SLN) status.
Main Methods:
- Immunohistochemistry was used to assess AXL and RIPK3 expression in 108 primary MM samples.
- Associations with clinical variables, SLN metastasis, and tumor-infiltrating lymphocytes (TILs) were analyzed.
- Logistic regression and ROC analysis were performed for predictive value assessment.
Main Results:
- AXL immunoreactivity was detected in 28% of tumors; RIPK3 in 16%.
- AXL-positive primary MM was significantly associated with SLN metastasis (p < 0.0001).
- AXL and Breslow depth were strong predictors of positive SLN status (AUC = 0.96).
Conclusions:
- AXL expression is a potential biomarker for predicting SLN metastasis in MM.
- AXL warrants further investigation for risk assessment and patient management in MM.
- RIPK3 expression showed no significant association with clinical variables in this cohort.
