Department of Thoracic Surgery, Thoraxklinik, Heidelberg University, Heidelberg, Germany.
Institute of Pathology, Heidelberg University, Heidelberg, Germany.
Lung Cancer. 2018 Apr;118:76-82. doi: 10.1016/j.lungcan.2018.02.003. Epub 2018 Feb 6.
Large cell neuroendocrine carcinoma of the lung (LCNEC) is associated with an unfavorable prognosis and only few patients are eligible for surgery. In most patients, chemotherapy is recommended alone or in addition to resection. Novel immunotherapies blocking the PD-L1 pathway have been introduced into therapeutic regimens for NSCLC with great success. In order to evaluate a possible efficacy of an anti-PD-L1 therapy, we analyzed the frequency of PD-L1 expression in LCNEC.
We retrospectively reviewed data from 76 patients with LCNEC treated in our institution between 1998 and 2010. The expression of PD-L1 was examined on the tumor cells and the tumor surrounding tissue by immunohistochemistry. An expression of >1% was considered as positive. Statistical analysis was performed to determine significant predictors for survival.
56 of 76 patients with LCNEC were treated with a potentially therapeutic surgical approach. Tumor-specific survival (TSS) of the entire cohort was 29% at five years. 17 patients (22.3%) had PD-L1 positive tumors and 12 of these had no additional PD-L1 expression in the adjacent immune cell infiltrate. Tumor-flanking immune cells were found PD-L1 positive 28 patients; 16 of these had no additional expression on the tumor cells. The most considerable difference in survival was found when comparing patients with isolated PD-L1 expression on tumor cells and PD-L1 negative immune cell infiltrate to their counterpart (positive immune-cell infiltrate and PD-L1 negative tumor cell surface; 5-year TSS: 0% vs. 60%; p < 0.017).
PD-L1 expression in LCNEC was associated with poorer survival whereas PD-L1 expression in the tumor microenvironment seemed to have a beneficial effect. Therapeutic approaches have to be evaluated in future.
肺大细胞神经内分泌癌（LCNEC）预后不良，只有少数患者适合手术。大多数患者建议单独化疗或联合手术。新型免疫疗法阻断 PD-L1 通路已被引入 NSCLC 的治疗方案，并取得了巨大成功。为了评估抗 PD-L1 治疗的可能疗效，我们分析了 LCNEC 中 PD-L1 的表达频率。
我们回顾性分析了 1998 年至 2010 年期间在我院治疗的 76 例 LCNEC 患者的数据。通过免疫组织化学法检测肿瘤细胞和肿瘤周围组织中 PD-L1 的表达。>1%的表达被认为是阳性。进行统计学分析以确定生存的显著预测因素。
76 例 LCNEC 患者中有 56 例接受了潜在治疗性手术治疗。整个队列的肿瘤特异性生存率（TSS）为 5 年时的 29%。17 例（22.3%）患者的肿瘤存在 PD-L1 阳性，其中 12 例肿瘤旁免疫细胞浸润无额外 PD-L1 表达。28 例肿瘤旁免疫细胞 PD-L1 阳性，其中 16 例肿瘤细胞无额外表达。当比较肿瘤细胞 PD-L1 单独表达且免疫细胞浸润 PD-L1 阴性的患者与对照组（免疫细胞浸润 PD-L1 阳性且肿瘤细胞 PD-L1 阴性）时，生存差异最大（5 年 TSS：0%对 60%；p<0.017）。
LCNEC 中 PD-L1 的表达与较差的生存相关，而肿瘤微环境中的 PD-L1 表达似乎有有益的影响。未来需要评估治疗方法。
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