Nicolè Lorenzo, Cappello Filippo, Cappellesso Rocco, Piccin Luisa, Ventura Laura, Guzzardo Vincenza, Del Fiore Paolo, Chiarion-Sileni Vanna, Dei Tos Angelo Paolo, Mocellin Simone, Fassina Ambrogio
Department of Medicine (DIMED), University of Padova, Padova, Italy.
Unit of Surgical Pathology & Cytopathology, Ospedale dell'Angelo, Mestre, Italy.
Front Oncol. 2021 Oct 21;11:728319. doi: 10.3389/fonc.2021.728319. eCollection 2021.
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.
恶性黑色素瘤（MM）是最致命的皮肤癌。AXL是一种酪氨酸激酶受体，参与多种致癌过程，可能通过下调坏死性凋亡相关驱动因子RIPK3在MM中阻断坏死性凋亡（一种受调控的细胞死亡机制）发挥作用。本研究的目的是评估AXL和RIPK3在108例原发性皮肤MM中的表达的临床影响。评估了AXL和RIPK3免疫反应性与临床病理变量、前哨淋巴结状态和肿瘤浸润淋巴细胞（TILs）之间的关联。AXL和RIPK3在肿瘤细胞中的免疫反应性分别在30例（28%；范围5%-80%）和17例（16%；范围5%-50%）中检测到。61例患者中有14例在前哨淋巴结中检测到转移，这些转移与原发性肿瘤中AXL阳性免疫反应性相关（p<0.0001）。未发现AXL与TILs之间存在关联。RIPK3免疫反应性与任何变量均无关联。最终的逻辑回归分析显示，Breslow和AXL阳性免疫反应性是前哨淋巴结阳性状态的更强预测指标[受试者操作特征曲线（AUC）下面积为0.96]。AXL可能是MM风险评估的潜在新生物标志物，值得在更大规模的研究中进一步研究。
