Dataset Information

RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study.

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.

SUBMITTER: Nicole L

PROVIDER: S-EPMC8566987 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study.

Nicolè Lorenzo L Cappello Filippo F Cappellesso Rocco R Piccin Luisa L Ventura Laura L Guzzardo Vincenza V Del Fiore Paolo P Chiarion-Sileni Vanna V Dei Tos Angelo Paolo AP Mocellin Simone S Fassina Ambrogio A

Frontiers in oncology 20211021

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, sent ...[more]

PMID: 34745951

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Project description:ImportanceA neural network-based model (i31-GEP-SLNB) that uses clinicopathologic factors (thickness, mitoses, ulceration, patient age) plus molecular analysis (31-gene expression profiling) has become commercially available to guide selection for sentinel lymph node (SLN) biopsy in cutaneous melanoma, but its clinical utility is not well characterized.ObjectiveTo determine if use of the i31-GEP-SLNB model is associated with clinical benefit when used to select patients for SLN biopsy.Design, setting, and participantsThis decision-analytic study used data derived from a published external validation study of the i31-GEP-SLNB prediction model. Participants included patients with primary cutaneous melanoma.Main outcomes and measuresThe primary outcome was the net benefit associated with using the i31-GEP-SLNB model for SLN biopsy selection compared with other selection strategies (SLN biopsy for all patients and SLN biopsy for no patients) at a 5% risk threshold. Analyses were stratified by American Joint Committee on Cancer (AJCC) T category. The reduction in the number of avoidable SLN biopsies and relative utility were also calculated.ResultsCompared with other SLN biopsy selection strategies, use of the i31-GEP-SLNB model had greater net benefit for patients with T1b (+0.012), T2a (+0.002), and T2b melanoma (+0.002) but not for those with high-risk T1a (-0.003) disease. The improvement in relative utility was +22% in patients with T1b, +1% in T2a, and +2% in T2b melanoma. Compared with SLN biopsy for all patients, use of the model would equate to a 23% decrease in SLN biopsies among patients with T1b disease without an SLN metastasis with no increase in the number of patients with an SLN metastasis left untreated; among patients with T2a and T2b melanoma, the net decrease in avoidable biopsies compared with SLN biopsy for all was 3% and 4%, respectively.Conclusions and relevanceThe findings of this decision-analytic study suggest that i31-GEP SLNB has significant potential for risk-stratifying patients with T1b melanoma if using a 5% risk threshold; its role among patients with T1a and T2 melanoma or using other risk thresholds requires further study. A prospective validation study confirming the added clinical benefit and cost-effectiveness of i31-GEP-SLNB compared with free clinicopathologic-based prediction models is needed in patients with T1b melanoma.

Dataset Information

RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study.

Publications

RIPK3 and AXL Expression Study in Primary Cutaneous Melanoma Unmasks AXL as Predictor of Sentinel Node Metastasis: A Pilot Study.

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