Department of Pathology, Aydın Adnan Menderes University Faculty of Medicine, Aydın, Turkey.
Department of Pathology, Aydın Adnan Menderes University Faculty of Medicine, Aydın, Turkey.
Pathol Res Pract. 2024 Aug;260:155463. doi: 10.1016/j.prp.2024.155463. Epub 2024 Jul 14.
The primary tumor and it's metastases show heterogeneity in molecular studies for targeted therapies in Non-Small Cell Lung Cancer(NSCLC), the leading cause of cancer-related deaths worldwide. The study aimed to identify somatic mutations in biopsies from NSCLC patients' metastatic organs using Next-Generation Sequencing(NGS) and examine their association with clinicopathological parameters.
The study included 128 NSCLC patients and, NGS was performed on tumor biopsies from different metastatic organs at Molecular Pathology laboratory of the Department of Medical Pathology in Aydın Adnan Menderes University Faculty of Medicine. The age, gender, histopathological diagnoses, metastatic organs, smoking and mutation status were all recorded, along with the analysis results of 72 genes and 4149 primers in the panel of the NGS system.
53.9 % of the cases had a history of smoking and patients with brain metastases had a higher smoking rate(p=0.000). The most common occurrence(39.8 %) was lymph node metastasis, followed by brain(19.5 %). There was a strong correlation between mutation presence and metastasis in the liver(p=0.012), bone(p=0.002), and pleura(p=0.008). Smokers had a higher frequency of KRAS(p=0.000) and TP53(p=0.001) mutations. Brain metastases showed a statistically significant NF1 mutation(p=0.001), while the liver exhibited a significant BRAF mutation(p=0.000). NF1-TP53, PTEN-TP53 and NF1-PTEN were the most common concomitant mutations and, the brain was the most common metastatic organ in which they occurred.
Our results suggest prizing assessing detected mutations, in the prediction, follow-up and management of metastases, especially in patients with lung adenocarcinoma. The assessment also needs to consider the tumor's mutation status in metastatic organs. New therapeutic agents targeting NF1 mutations will be available in the future to treat NSCLC, especially in metastases.
在非小细胞肺癌（NSCLC）的靶向治疗中，原发肿瘤及其转移灶在分子研究中表现出异质性，这是全球癌症相关死亡的主要原因。本研究旨在使用下一代测序（NGS）在 NSCLC 患者转移器官的活检中鉴定体细胞突变，并研究其与临床病理参数的关系。
该研究纳入了 128 名 NSCLC 患者，在阿德南·曼德雷塞大学医学院医学病理学系的分子病理学实验室对来自不同转移器官的肿瘤活检进行了 NGS。记录了患者的年龄、性别、组织病理学诊断、转移器官、吸烟情况和突变状态，以及 NGS 系统面板中 72 个基因和 4149 个引物的分析结果。
53.9%的病例有吸烟史，脑转移患者的吸烟率更高（p=0.000）。最常见的转移部位是淋巴结（39.8%），其次是脑（19.5%）。突变的存在与肝（p=0.012）、骨（p=0.002）和胸膜（p=0.008）转移之间存在很强的相关性。吸烟者 KRAS（p=0.000）和 TP53（p=0.001）突变的频率更高。脑转移显示 NF1 突变具有统计学意义（p=0.001），而肝脏显示 BRAF 突变具有统计学意义（p=0.000）。NF1-TP53、PTEN-TP53 和 NF1-PTEN 是最常见的伴随突变，且脑是最常见的发生转移的器官。
我们的结果表明，在预测、随访和管理转移瘤时，需要评估检测到的突变，尤其是在肺腺癌患者中。评估还需要考虑转移器官中肿瘤的突变状态。未来将有针对 NF1 突变的新治疗药物用于治疗 NSCLC，特别是针对转移瘤。
