Lezcano Cecilia, Luo Li, Shen Ronglai, Orlow Irene, Thomas Nancy E, Berwick Marianne, Busam Klaus J
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Internal Medicine and the University of New Mexico Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, USA.
EJC Skin Cancer. 2024 Dec;2. doi: 10.1016/j.ejcskn.2024.100274. Epub 2024 Oct 24.
To evaluate the relation between solar elastosis and tumor mutation burden (TMB) in a large clinically annotated cohort of stage II and III melanoma patients.
Primary cutaneous melanomas from 469 AJCC (8 edition) stage II and III patients with clinical annotation including outcome at 5 years of diagnosis were histopathologically evaluated for solar elastosis. Next-generation sequencing assay MSK-IMPACT was employed to determine TMB. Analysis by Fisher's exact test, chi-square, and Kruskal-Wallis were performed, as well as uni- and multivariate logistic regression.
Tumors stratified by low and high TMB showed marked and statistically significant differences in presence and extent of associated solar elastosis. Lower risk patient stage (II versus III by AJCC 8 edition) as well as better 5-year melanomaspecific survival (as binary variable of controls-survivors versus cases-dead of disease at 5 years of diagnosis) were associated with severe solar elastosis. On univariate and multivariate logistic regression models, severe solar elastosis predicted significantly decreased odds of dying of melanoma within 5 years of diagnosis (OR 0.60, 95 % CI 0.39-0.89; and OR 0.42, 95 % CI 0.20-0.83, respectively; both p<0.05).
The association of solar elastosis to TMB and 5-year melanoma specific survival points to its potential as a biomarker of clinical relevance that can be assessed by routine histopathology.
在一个具有大量临床注释的II期和III期黑色素瘤患者队列中,评估日光性弹力组织变性与肿瘤突变负荷(TMB)之间的关系。
对469例AJCC(第8版)II期和III期原发性皮肤黑色素瘤患者进行组织病理学评估,以确定日光性弹力组织变性情况,这些患者具有临床注释,包括诊断后5年的预后。采用二代测序检测方法MSK-IMPACT来确定TMB。进行了Fisher精确检验、卡方检验和Kruskal-Wallis分析,以及单因素和多因素逻辑回归分析。
根据TMB高低分层的肿瘤在相关日光性弹力组织变性的存在和程度上显示出显著且具有统计学意义的差异。较低风险的患者分期(AJCC第8版II期与III期)以及较好的5年黑色素瘤特异性生存率(作为诊断后5年对照组-幸存者与病例-死于疾病的二元变量)与严重的日光性弹力组织变性相关。在单因素和多因素逻辑回归模型中,严重的日光性弹力组织变性显著预测了诊断后5年内死于黑色素瘤的几率降低(OR分别为0.60,95%CI 0.39-0.89;以及OR 0.42,95%CI 0.20-...