Ichiki Yoshinobu, Matsumiya Hiroki, Mori Masataka, Kanayama Masatoshi, Nabe Yusuke, Taira Akihiro, Shinohara Shinji, Kuwata Taiji, Takenaka Masaru, Hirai Ayako, Imanishi Naoko, Yoneda Kazue, Noguchi Hiroshi, Shimajiri Shohei, Fujino Yoshihisa, Nakayama Toshiyuki, Tanaka Fumihiro
Second Department of Surgery, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Department of Pathology and Cell Biology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
J Thorac Dis. 2018 Dec;10(12):6912-6920. doi: 10.21037/jtd.2018.11.115.
Pulmonary neuroendocrine tumor (NET) occurs with 20% of all lung cancers, and there are a limited number of literatures about the molecular aberrations, treatment and prognosis; especially in resected cases, as the operation indication for large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) is rare due to their aggressive behaviors. We investigated the relationship between postoperative survival and molecular expression patterns of pulmonary NET to establish a more effective treatment strategy.
In the present study, the curative surgical resection of pulmonary NET was reviewed retrospectively. A total of 105 patients with pulmonary NET, who underwent complete resection between 1978 and 2016, were subjected to analysis with respect to histological characterization and clinical behaviors of pulmonary NET using immunohistochemistry (IHC) of neuroendocrine markers and programmed cell death-ligand 1 (PD-L1).
The pathological types included 67 SCLC, 18 LCNEC, 14 typical carcinoids (TCs) and 6 atypical carcinoids (ACs). The ACs had significantly worse prognosis than TCs. PD-L1 expression ratio in SCLC/LCNEC/TC/AC was 26.1%/50%/15.4%/20%, respectively. However, it was not significantly correlated with each prognosis. Therefore, the SCLC patients were analyzed, the overall 5-year survival of SCLC patients was found to be 47.3%. In the univariate analysis of the molecular expression of SCLC, neuroendocrine markers such as chromogranin-A (CGA) and synaptophysin (SYN) showed poor prognosis, albeit without significant differences.
The neuroendocrine markers such as CGA and SYN might assist the prediction of prognosis and probably influence the decision for adjuvant chemotherapy or follow-up intervals after surgery in SCLC patients; however additional studies are essential.
肺神经内分泌肿瘤(NET)占所有肺癌的20%,关于其分子异常、治疗及预后的文献数量有限;尤其是在手术切除病例中,由于大细胞神经内分泌癌(LCNEC)和小细胞肺癌(SCLC)侵袭性强,手术指征罕见。我们研究了肺NET术后生存与分子表达模式之间的关系,以建立更有效的治疗策略。
在本研究中,对肺NET的根治性手术切除进行了回顾性分析。1978年至2016年间接受完全切除的105例肺NET患者,采用神经内分泌标志物和程序性细胞死亡配体1(PD-L1)的免疫组织化学(IHC)方法,对肺NET的组织学特征和临床行为进行分析。
病理类型包括67例SCLC、18例LCNEC、14例典型类癌(TC)和6例非典型类癌(AC)。AC的预后明显比TC差。SCLC/LCNEC/TC/AC中PD-L1的表达率分别为26.1%/50%/15.4%/20%。然而,它与各预后均无显著相关性。因此,对SCLC患者进行分析,发现SCLC患者的总体5年生存率为47.3%。在SCLC分子表达的单因素分析中,嗜铬粒蛋白A(CGA)和突触素(SYN)等神经内分泌标志物显示预后较差,尽管无显著差异。
CGA和SYN等神经内分泌标志物可能有助于预测SCLC患者的预后,并可能影响辅助化疗决策或术后随访间隔;然而,还需要更多研究。