Xu Fengkai, Chen Ke, Lu Chunlai, Gu Jie, Zeng Haiying, Xu Yifan, Ji Yuan, Ge Di
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, PR China.
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, PR China.
Transl Oncol. 2019 Apr;12(4):646-655. doi: 10.1016/j.tranon.2019.01.004. Epub 2019 Feb 25.
Large cell neuroendocrine carcinoma (LCNEC) was categorized into pulmonary neuroendocrine tumors (NETs) according to the World Health Organization classification guideline. However, LCNEC patients often received the chemotherapy regimens similar to non-small cell lung carcinoma (NSCLC) in advanced stage and the therapeutic effect was unsatisfactory. Therefore, this study aimed to investigate the hidden clinical features, prognosis and immunoprofile of the LCNEC, compared with carcinoid and SCLC, to explore whether LCNEC shares similarity with SCLC and potential treatment approaches could be revealed.
One hundred seventeen pulmonary NETs cases were retrospectively retrieved in this study. The Kaplan-Meier estimator was employed to draw survival curves. Immunohistochemistry was applied to detect NET-related markers expression.
In clinical features, compared with carcinoid, LCNEC patients were older, more commonly in male and advanced stage. The parallel phenomena were also found in the high-grade subgroup when compared with the low- to intermediate-grade one. In survival analysis, the 5-year overall survival of LCNECs was 59.1%, which was poorer than that of carcinoids, but better than that of SCLCs. Immunohistochemistry showed that p53 and PTEN functional inactivation, up-regulation of CD117 expression, down-regulation of SSR2A and SSR5 expression were commonly involved in LCNECs when compared with carcinoids, or in the high-grade subgroup when compared with the low- to intermediate-grade one. However, no significant difference was found in the comparison between LCNECs and SCLCs, or NSCLCs and SCLCs.
In clinical features, survival and immunoprofile, LCNEC showed more similarity with SCLC rather than carcinoid, which might guide novel therapy for pulmonary NETs.
根据世界卫生组织分类指南，大细胞神经内分泌癌（LCNEC）被归类为肺神经内分泌肿瘤（NETs）。然而，LCNEC患者在晚期常接受与非小细胞肺癌（NSCLC）相似的化疗方案，治疗效果并不理想。因此，本研究旨在探讨LCNEC与类癌和小细胞肺癌（SCLC）相比潜在的临床特征、预后及免疫表型，以探究LCNEC是否与SCLC具有相似性，并揭示潜在的治疗方法。
本研究回顾性检索了117例肺NETs病例。采用Kaplan-Meier估计法绘制生存曲线。应用免疫组织化学检测NET相关标志物的表达。
在临床特征方面，与类癌相比，LCNEC患者年龄更大，男性更常见，且多处于晚期。与低至中级别亚组相比，高级别亚组也存在类似情况。在生存分析中，LCNEC的5年总生存率为59.1%，低于类癌，但高于SCLC。免疫组织化学显示，与类癌相比，LCNEC中p53和PTEN功能失活、CD117表达上调、SSR2A和SSR5表达下调较为常见；与低至中级别亚组相比，高级别亚组也有类似情况。然而，LCNEC与SCLC、NSCLC与SCLC之间的比较未发现显著差异。
在临床特征、生存情况和免疫表型方面，LCNEC与SCLC的相似性高于类癌，这可能为肺NETs的新治疗方法提供指导。
