Li Zhenhua, Lv Huilai, Zhang Fan, Zhu Ziming, Guo Qiang, Wang Mingbo, Huang Chao, Guo Lijie, Meng Fanfei, Tian Ziqiang
Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Thoracic Surgery, The First Hospital of Xingtai, Xingtai, China.
PeerJ. 2024 Jan 31;12:e16808. doi: 10.7717/peerj.16808. eCollection 2024.
Multiple lung cancers may present as multiple primary lung cancers (MPLC) or intrapulmonary metastasis (IPM) with variations in clinical stage, treatment, and prognosis. However, the existing differentiation criteria based on histology do not fully meet the clinical needs. Next-generation sequencing (NGS) may play an important role in assisting the identification of different pathologies. Here, we extended the relevant data by combining histology and NGS to develop detailed identification criteria for MPLC and IPM.
Patients with lung cancer (each patient had ≥2 tumors) were enrolled in the training ( = 22) and validation ( = 13) cohorts. Genomic profiles obtained from 450-gene-targeted NGS were analyzed, and the new criteria were developed based on our findings and pre-existing Martini & Melamed criteria and molecular benchmarks.
The analysis of the training cohort indicated that patients identified with MPLC had no (or <2) trunk or shared mutations. However, 98.02% of mutations were branch mutations, and 69.23% of MPLC had no common mutations. In contrast, a higher percentage of trunk (33.08%) or shared (9.02%) mutations were identified in IPM, suggesting significant differences among mutated components. Subsequently, eight MPLC and five IPM cases were identified in the validation cohort, aligning with the independent imaging and pathologic distinction. Overall, the percentage of trunk and shared mutations was higher in patients with IPM than in patients with MPLC. Based on these results and the establishment of new determination criteria for MPLC and IPM, we emphasize that the type and number of shared variants based on histologic consistency assist in identification.
Determining genetic alterations may be an effective method for differentiating MPLC and IPM, and NGS can be used as a valuable assisting tool.
多发性肺癌可能表现为多原发性肺癌（MPLC）或肺内转移（IPM），其临床分期、治疗和预后存在差异。然而，现有的基于组织学的鉴别标准不能完全满足临床需求。二代测序（NGS）可能在辅助鉴别不同病理类型方面发挥重要作用。在此，我们通过结合组织学和NGS扩展相关数据，以制定MPLC和IPM的详细鉴别标准。
纳入肺癌患者（每位患者有≥2个肿瘤）进入训练队列（n = 22）和验证队列（n = 13）。分析从450基因靶向NGS获得的基因组图谱，并根据我们的研究结果以及先前存在的Martini & Melamed标准和分子基准制定新的标准。
训练队列分析表明，被鉴定为MPLC的患者没有（或<2个）主干或共享突变。然而，98.02%的突变是分支突变，69.23%的MPLC没有共同突变。相比之下，在IPM中鉴定出更高比例的主干突变（33.08%）或共享突变（9.02%），表明突变成分之间存在显著差异。随后，在验证队列中鉴定出8例MPLC和5例IPM病例，与独立的影像学和病理学鉴别结果一致。总体而言，IPM患者的主干和共享突变百分比高于MPLC患者。基于这些结果以及建立的MPLC和IPM新判定标准，我们强调基于组织学一致性的共享变异的类型和数量有助于鉴别。
确定基因改变可能是区分MPLC和IPM的有效方法，NGS可作为有价值的辅助工具。
