Epidermal autophagy and beclin 1 regulator 1 and loricrin: a paradigm shift in the prognostication and stratification of the American Joint Committee on Cancer stage I melanomas
Epidermal autophagy and beclin 1 regulator 1 and loricrin: a paradigm shift in the prognostication and stratification of the American Joint Committee on Cancer stage I melanomas
复制标题
DOI：
10.1111/bjd.18086
复制
发表时间：
2020-01-01
影响因子：
10.3
通讯作者：
Lovat, P. E.
中科院分区：
文献类型：
--
作者：
Ellis, R.;Tang, D.;Lovat, P. E.
背景更新的美国癌症联合委员会（AJCC）黑色素瘤分期标准仍然无法识别高风险的I期肿瘤亚群。目的确定表皮自噬和beclin 1调节因子1（AMBRA 1）/兜甲蛋白（AMLo）的效用。AMBRA 1表达作为AJCC I期皮肤黑色素瘤预后生物标志物。方法在76例AJCC I期患者的回顾性发现队列中评估瘤周AMBRA 1表达。黑素瘤。AMLo表达与12年的临床结局相关，结果在76个AJCC I期肿瘤的发现组群中，覆盖原发性黑素瘤的表皮中AMBRA 1表达降低与81.5%对100%的7年无病生存率（DFS）相关。维持AMBRA 1的存活率（P < 0.081）。根据AMLo半定量分析的免疫组织化学方案，在AJCC I期黑色素瘤的验证（n = 218）和资格队列（n = 161）中进行分析。联合队列分析显示，AMLo低风险组（n = 239）的DFS率为98.3%，而AMLo高风险组为85.4%（n = 140; P < 0.001）。亚队列多变量分析显示，AMLo风险比（HR）为4.04 [95%置信区间（CI）1.69-9.66; P = 0.002]是比Breslow深度更强的DFS预测因子。（HR 2.97，95% CI 0.93-9.56; P = 0.068）。结论原发性AJCC I期黑色素瘤表皮AMLo表达缺失，独立于Breslow深度的风险肿瘤子集。
Background The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high-risk stage I tumour subsets.Objectives To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma.Methods Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas.Results Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7-year disease-free survival (DFS) rate of 81 .5% vs. 100% survival with maintained AMBRA1 (P < 0.081). Following an immunohistochemistry protocol for semi-quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98.3% in the AMLo low-risk group (n = 239) vs. 85.4% in the AMLo high-risk cohort (n = 140; P < 0.001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4.04 [95% confidence interval (CI) 1.69-9.66; P = 0.002] is a stronger predictor of DFS than Breslow depth (HR 2.97, 95% CI 0.93-9.56; P = 0.068) in stage IB patients.Conclusions Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high-risk tumour subsets independently of Breslow depth.