Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; Department of Pathology, Kashgar Prefecture Second People's Hospital, Urumqi, China.
Lung Cancer. 2018 Feb;116:30-37. doi: 10.1016/j.lungcan.2017.12.009. Epub 2017 Dec 15.
Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents a rare entity in lung cancer with dismal prognosis. In the present study, we investigated whether there are significant differences between central and peripheral tumors of LCNEC, in terms of clinicopathologic features, genomic profiles, and survival.
A total of 126 cases of LCNEC were included. The tumors with invasion of the segmental and/or lobar bronchus were classified as central LCNEC and those without as peripheral LCNEC. EGFR/BRAF/Kras mutations and ALK/ROS1 translocations were detected. Overall survival (OS) was evaluated by the Kaplan-Meier plots.
The majority of LCNEC proved to be of the peripheral type (64.3%, 81/126). Central tumors were associated with smoking habit (p = 0.047), higher TNM-stage (p = 0.014) and larger tumor size (p < 0.001). Expression of neuroendocrine markers (CD56, CGA, and SYN) was not significantly different by tumor location but central tumors had higher serum levels of NSE (p = 0.004). Peripheral tumors had a higher incidence of EGFR mutations (18.8% vs. 0%, p = 0.023). ROS1 translocation was detected in 1 patient with peripheral LCNEC. RB1 protein was more frequently expressed in peripheral tumor than central tumor. The median OS was 3.71 years in the entire cohort. Peripheral tumors had better survival compared with central tumors (median OS: 4.04 vs. 1.51 years, p < 0.001). Multivariate analyses demonstrated tumor location (hazard ratio [HR], 6.07, 95% confidence interval [CI], 1.57-23.44, p = 0.009), resection status (HR, 6.58, 95% CI, 1.92-22.51, p = 0.003) and EGFR mutational status (HR, 0.18, 95% CI, 0.04-0.75, p = 0.018) were independent prognostic factors for OS.
Primary tumor location of LCNEC, divided into central and peripheral type, has distinct clinicopathologic features, genomic characteristics and survival. These differences are likely due to differences in the origin cells and pathogenesis of these tumors.
肺大细胞神经内分泌癌（LCNEC）是肺癌中一种罕见的实体肿瘤，预后较差。本研究旨在探讨 LCNEC 中央型与周围型肿瘤在临床病理特征、基因组谱和生存方面是否存在显著差异。
共纳入 126 例 LCNEC 患者。肿瘤侵犯段或叶支气管者为中央型 LCNEC，未侵犯者为周围型 LCNEC。检测 EGFR/BRAF/Kras 基因突变和 ALK/ROS1 易位。采用 Kaplan-Meier 法评估总生存期（OS）。
大多数 LCNEC 为周围型（64.3%，81/126）。中央型肿瘤与吸烟史相关（p=0.047），TNM 分期较高（p=0.014），肿瘤较大（p<0.001）。神经内分泌标志物（CD56、CGA 和 SYN）的表达与肿瘤位置无显著差异，但中央型肿瘤的血清 NSE 水平较高（p=0.004）。周围型 LCNEC 患者 EGFR 突变发生率较高（18.8% vs. 0%，p=0.023）。1 例周围型 LCNEC 患者检测到 ROS1 易位。RB1 蛋白在周围型肿瘤中的表达较中央型肿瘤更为频繁。全队列的中位 OS 为 3.71 年。与中央型肿瘤相比，周围型肿瘤的生存更好（中位 OS：4.04 与 1.51 年，p<0.001）。多因素分析显示肿瘤位置（HR，6.07；95%CI，1.57-23.44；p=0.009）、切除状态（HR，6.58；95%CI，1.92-22.51；p=0.003）和 EGFR 突变状态（HR，0.18；95%CI，0.04-0.75；p=0.018）是 OS 的独立预后因素。
LCNEC 的原发肿瘤位置可分为中央型和周围型，具有明显的临床病理特征、基因组特征和生存差异。这些差异可能归因于这些肿瘤起源细胞和发病机制的不同。
