Department of Pulmonary Diseases, GROW School for Oncology & Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Clin Cancer Res. 2018 Jan 1;24(1):33-42. doi: 10.1158/1078-0432.CCR-17-1921. Epub 2017 Oct 24.
Previous genomic studies have identified two mutually exclusive molecular subtypes of large-cell neuroendocrine carcinoma (LCNEC): the mutated (mostly comutated with ) and the wild-type groups. We assessed whether these subtypes have a predictive value on chemotherapy outcome. Clinical data and tumor specimens were retrospectively obtained from the Netherlands Cancer Registry and Pathology Registry. Panel-consensus pathology revision confirmed the diagnosis of LCNEC in 148 of 232 cases. Next-generation sequencing (NGS) for and genes, as well as IHC for RB1 and P16 was performed on 79 and 109 cases, respectively, and correlated with overall survival (OS) and progression-free survival (PFS), stratifying for non-small cell lung cancer type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) and platinum-etoposide (SCLC-PE). mutation and protein loss were detected in 47% ( = 37) and 72% ( = 78) of the cases, respectively. Patients with wild-type LCNEC treated with NSCLC-GEM/TAX had a significantly longer OS [9.6; 95% confidence interval (CI), 7.7-11.6 months] than those treated with SCLC-PE [5.8 (5.5-6.1); = 0.026]. Similar results were obtained for patients expressing RB1 in their tumors ( = 0.001). RB1 staining or P16 loss showed similar results. The same outcome for chemotherapy treatment was observed in LCNEC tumors harboring an mutation or lost RB1 protein. Patients with LCNEC tumors that carry a wild-type gene or express the RB1 protein do better with NSCLC-GEM/TAX treatment than with SCLC-PE chemotherapy. However, no difference was observed for mutated or with lost protein expression. .
先前的基因组研究已经确定了大细胞神经内分泌癌（LCNEC）两种互斥的分子亚型： 突变型（大多与 同时突变）和 野生型。我们评估了这些亚型对化疗结果是否具有预测价值。临床数据和肿瘤标本从荷兰癌症登记处和病理登记处获得。小组共识病理修订确认了 232 例中的 148 例为 LCNEC。对 79 例和 109 例分别进行了 基因和 基因的下一代测序（NGS），以及 RB1 和 P16 的 IHC，并与总生存（OS）和无进展生存（PFS）相关，分层为非小细胞肺癌型化疗，包括铂+吉西他滨或紫杉类（NSCLC-GEM/TAX）和铂依托泊苷（SCLC-PE）。分别检测到 47%（=37）和 72%（=78）的病例中存在 突变和蛋白缺失。用 NSCLC-GEM/TAX 治疗的 野生型 LCNEC 患者的 OS[9.6；95%置信区间（CI），7.7-11.6 个月]明显长于用 SCLC-PE 治疗的患者[5.8（5.5-6.1）；=0.026]。在肿瘤中表达 RB1 的患者也获得了类似的结果（=0.001）。RB1 染色或 P16 缺失显示出相似的结果。携带 突变或丢失 RB1 蛋白的 LCNEC 肿瘤的化疗治疗结果也相同。携带 野生型 基因或表达 RB1 蛋白的 LCNEC 肿瘤患者，接受 NSCLC-GEM/TAX 治疗比接受 SCLC-PE 化疗效果更好。然而，对于 突变或蛋白表达丢失的患者，未观察到差异。LCNEC 肿瘤携带野生型 基因或表达 RB1 蛋白的患者，用 NSCLC-GEM/TAX 治疗比用 SCLC-PE 化疗效果更好。然而，对于 突变或蛋白表达丢失的患者，未观察到差异。
