Department of Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pa.
Department of Pathology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pa.
J Thorac Cardiovasc Surg. 2020 Aug;160(2):e71-e79. doi: 10.1016/j.jtcvs.2019.11.126. Epub 2019 Dec 20.
Multifocal non-small cell lung cancer has historically been separated into synchronous primary lung cancers or intrapulmonary metastases with the use of histopathology. We hypothesize that using targeted next-generation sequencing of key driver mutations in multifocal non-small cell lung cancer will improve our ability to differentiate intrapulmonary metastases from synchronous primary lung cancers.
We identified patients who underwent surgery for non-small cell lung cancer between 2013 and 2018 with multifocal tumors. Archived specimens were reviewed with a 4-gene next-generation sequencing panel identifying mutations of EGFR, KRAS, BRAF, and NRAS. Synchronous primary lung cancers were classified as lesions with different histopathologic subtypes or driver mutations. Tests of hypotheses were performed with the Fisher exact test. Calculations were performed in Stata (v13.0; StataCorp LLC, College Station, Tex).
A total of 18 patients had non-small cell lung cancer tumor specimens (n = 41) available from 2 or more sites. The pathologic diagnosis was predominantly adenocarcinoma (39/41 specimens). We detected a driver mutation in 68.3% (28/41) of all tumors. The most common mutations observed were in KRAS (n = 17/41) and EGFR (n = 7/41). Eleven patients had synchronous primary lung cancers, and 4 patients had intrapulmonary metastases based on combined histopathologic and molecular profiling results. Three lacked driver mutations in either lesion. Eight synchronous primary lung cancers (8/18, 44%) were downstaged when compared with their original diagnosis (P = .08). Of these, 4 patients received adjuvant chemotherapy unnecessarily in hindsight.
Molecular non-small cell lung cancer profiling using a 4-gene next-generation sequencing panel allows for better distinction between synchronous primary lung cancers and intrapulmonary metastases than histopathology alone. Routine use of next-generation sequencing for multifocal lesions prevents unnecessary adjuvant treatment for patients with histologically similar synchronous primary lung cancers.
多灶性非小细胞肺癌（NSCLC）在临床上被分为同步性原发性肺癌或肺内转移，其诊断主要依靠组织病理学。我们假设，对多灶性 NSCLC 进行关键驱动基因突变的靶向下一代测序，将提高我们区分肺内转移和同步性原发性肺癌的能力。
我们鉴定了 2013 年至 2018 年间因多灶性肿瘤而行手术治疗的 NSCLC 患者。回顾性分析 4 基因下一代测序面板的存档标本，该面板可检测 EGFR、KRAS、BRAF 和 NRAS 基因突变。同步性原发性肺癌的定义为具有不同组织病理学亚型或驱动基因突变的病变。采用 Fisher 确切检验进行假设检验。计算在 Stata（v13.0；StataCorp LLC，College Station，Tex）中完成。
共有 18 例患者有 2 个或更多部位的 NSCLC 肿瘤标本（n=41）。病理诊断主要为腺癌（39/41 个标本）。我们在所有肿瘤的 68.3%（28/41）中检测到驱动突变。最常见的突变发生在 KRAS（n=17/41）和 EGFR（n=7/41）。11 例患者为同步性原发性肺癌，4 例患者为肺内转移，这一结果基于联合组织病理学和分子分析结果。有 3 例患者在两个病变中均未发现驱动突变。与最初诊断相比，8 例同步性原发性肺癌（18 例中的 8 例，44%）降级（P=0.08）。事后看来，这 4 例患者中有 4 例不必要地接受了辅助化疗。
与单纯组织病理学相比，使用 4 基因下一代测序面板进行非小细胞肺癌分子谱分析可更好地区分同步性原发性肺癌和肺内转移。对多灶性病变常规进行下一代测序，可防止对具有相似组织病理学表现的同步性原发性肺癌患者进行不必要的辅助治疗。
