Department of General Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Cancer Sci. 2018 Nov;109(11):3634-3642. doi: 10.1111/cas.13797. Epub 2018 Oct 6.
In patients presenting with synchronous or metachronous multiple lung cancer (MLC), it is important to distinguish between multiple primary lung cancer (MP) and intrapulmonary metastasis (IM). The present study was aimed at investigating the mutational profiles of synchronous/metachronous MLC and to compare the classification of paired tumors by multiplex gene mutation analysis with the histopathological evaluation. We carried out targeted sequencing of 20 lung cancer-related oncogenes using next-generation sequencing (NGS) in 82 tumors from 37 MLC patients who underwent surgical resection at our department. The patients were diagnosed as MP or IM cases based on the Martini and Melamed criteria, histopathological and gene mutational evaluations. Matching mutations between paired tumors was observed in 20 (54%) patients, who were diagnosed as IM cases by mutational evaluation. Patients who could not be clearly diagnosed by histopathological evaluation were classified as equivocal cases. Among the histopathological IM cases (n = 7), six (86%) were confirmed as IM cases also by mutational evaluation, and most of the paired tumors of these cases (n = 5) harbored multiple matching mutations. Among the histopathological MP cases (n = 17), mutational evaluation yielded a discordant diagnosis in eight (47%) cases. Of these, the paired tumors of four cases harbored multiple matching mutations, suggesting that the mutational diagnosis might be more suitable in these patients. Our findings suggest that multiplex mutational analysis could be a useful complementary tool for distinguishing between MP and IM in addition to histopathological evaluation.
在同时性或异时性多原发性肺癌（MLC）患者中，区分多原发性肺癌（MP）和肺内转移（IM）非常重要。本研究旨在探讨同步/异时性 MLC 的突变特征，并比较多重基因突变分析对配对肿瘤的分类与组织病理学评估的结果。我们对 37 例在我科行手术切除的 MLC 患者的 82 个肿瘤进行了 20 个肺癌相关致癌基因的靶向测序，这些患者均采用下一代测序（NGS）。根据 Martini 和 Melamed 标准、组织病理学和基因突变评估，将患者诊断为 MP 或 IM 病例。在 20 例（54%）可观察到配对肿瘤之间存在匹配突变的患者中，通过突变评估诊断为 IM 病例。通过组织病理学评估无法明确诊断的患者被归类为疑似病例。在组织学 IM 病例（n=7）中，通过突变评估证实 6 例（86%）为 IM 病例，且这些病例的大多数配对肿瘤（n=5）均存在多个匹配突变。在组织学 MP 病例（n=17）中，突变评估在 8 例（47%）病例中得出不一致的诊断。其中，4 例配对肿瘤存在多个匹配突变，提示这些患者的突变诊断可能更为合适。我们的研究结果表明，与组织病理学评估相比，多重突变分析除了可以作为一种有用的补充工具来区分 MP 和 IM。
