Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Thorac Cancer. 2021 Oct;12(20):2789-2795. doi: 10.1111/1759-7714.14126. Epub 2021 Aug 31.
Low-grade fetal adenocarcinoma of the lung (L-FLAC) is a rare subtype of lung adenocarcinoma with undetermined histological features and genetic abnormalities. In this study, we attempted to investigate the pathological characteristics and genomic profiles of L-FLAC.
Among 9839 cases of primary lung adenocarcinoma resected at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2011 and June 2016, three cases diagnosed with L-FLAC were selected. An immunohistochemical profile and whole exome sequencing (WES) using tumor and normal tissues was conducted. The last follow-up date of patients was January 2021.
Three cases diagnosed with L-FLAC were finally screened, suggesting a percentage of 0.03%. All three patients were male and diagnosed as stage I following radical lobectomy. The missense variant was found to be the major gene mutation type using WES. CTNNB1 and DICER1 were the two most frequent gene mutations. All cases demonstrated positive TTF-1 expression. In addition, two patients showed positive expression of β-catenin (nuclear/cytoplasmic expression), CgA and Sny. Negative expression of PD-L1 in tumor cells was observed in all three cases. One case with a relatively high tumor mutation burden (TMB) (2.18 mut/Mb) had an inferior overall survival of 11.5 months. However, the other two cases with a lower TMB (0.12 and 0.74 mut/Mb) still acquired disease-free status up to the last follow-up date.
L-FLAC has a specific molecular background which is different from lung adenocarcinoma. Furthermore, gene heterogeneity was found and might be the reason for a dramatically different prognosis in these L-FLAC patients.
低级别胎儿肺腺癌（L-FLAC）是一种罕见的肺腺癌亚型，具有不确定的组织学特征和遗传异常。本研究旨在探讨 L-FLAC 的病理特征和基因组特征。
在 2011 年 1 月至 2016 年 6 月期间，中国医学科学院北京协和医学院肿瘤医院共切除了 9839 例原发性肺腺癌患者，其中 3 例被诊断为 L-FLAC。采用免疫组化分析和肿瘤及正常组织的全外显子组测序（WES）进行检测。最后一次随访日期为 2021 年 1 月。
最终筛选出 3 例 L-FLAC 患者，占比为 0.03%。所有患者均为男性，行根治性肺叶切除术后分期为 I 期。WES 结果显示，错义突变是主要的基因突变类型。CTNNB1 和 DICER1 是最常见的基因突变类型。所有病例均表现出 TTF-1 阳性表达。此外，有 2 例患者β-连环蛋白（核/浆表达）、CgA 和 Sny 阳性表达。所有 3 例患者肿瘤细胞 PD-L1 均为阴性表达。1 例患者肿瘤突变负荷（TMB）较高（2.18 突变/Mb），总生存期为 11.5 个月。而另外 2 例 TMB 较低（0.12 和 0.74 突变/Mb）的患者，截至最后一次随访仍处于无疾病状态。
L-FLAC 具有不同于肺腺癌的特定分子背景。此外，本研究还发现了基因异质性，这可能是导致这些 L-FLAC 患者预后差异巨大的原因。
