Esophageal squamous cell carcinoma (ESCC) patients with a synchronous or metachronous lung tumor can be diagnosed with lung metastasis (LM) or a second primary tumor (SPT), but the accurate discrimination between LM and SPT remains a clinical dilemma. This study aimed to investigate the feasibility of using the whole-exome sequencing (WES) technique to distinguish SPT from LM./nMethods: We performed WES on 40 tumors from 14 patients, including 12 patients with double squamous cell carcinomas (SCCs) of the esophagus and lung (lymph node metastases were sequenced as internal controls) diagnosed as LM according to pathological information and 2 patients with paired primary ESCC and non-lung metastases examined as external controls./nResults: Shared genomic profiles between esophageal (T) and lung (D) tumors were observed in 7 patients, suggesting their clonal relatedness, thus indicating that the lung tumors of these patients should be LM. However, distinct genomic profiles between T and D tumors were observed in the other 5 patients, suggesting the possibility of SPTs that were likely formed through independent multifocal oncogenesis./nConclusions: Our data demonstrate the limitations and insufficiency of clinicopathological criteria and that WES could be useful in understanding the clonal relationships of multiple SCCs.

中文翻译：

---

使用全外显子组测序从食管鳞状细胞癌患者的肺转移中鉴定出第二原发肿瘤。

患有同步性或异时性肺肿瘤的食管鳞状细胞癌（ESCC）患者可以诊断为肺转移（LM）或第二原发肿瘤（SPT），但是LM和SPT之间的准确区分仍然是临床难题。这项研究旨在探讨使用全外显子测序（WES）技术将SPT与LM区分的可行性。方法：我们对14例患者中的40例肿瘤（包括12例双鳞癌）中的40例肿瘤进行了WES。根据病理信息将食管和肺（淋巴结转移作为内部对照）确定为LM，并将2例原发性ESCC和非肺转移配对的患者作为外部对照。在7例患者中发现了食管（T）和肺（D）肿瘤共有的基因组图谱，表明它们具有克隆相关性，因此表明这些患者的肺肿瘤应为LM。然而，在其他5例患者中，T和D肿瘤之间观察到了独特的基因组图谱，这表明SPT可能是通过独立的多灶性肿瘤发生而形成的。/n结论：我们的数据证明了临床病理学标准的局限性和不足，WES在理解多个SCC的克隆关系方面很有用。