Zhichao Liu1, Hengrui Liang1, Jie Lin2, Xiuyu Cai3, Zhenkui Pan4, Jun Liu1, Xiaohong Xie1, Caichen Li1, Bo Cheng1, Yi Zhao1, Jianxing He5, Wenhua Liang6. 1. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. 2. Department of Medical Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. 3. Department of General Internal Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. 4. Department of Oncology, Qingdao Municipal Hospital, Qingdao, China. 5. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. Electronic address: drjianxing.he@gmail.com. 6. Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China. Electronic address: liangwh1987@163.com.
Abstract
OBJECTIVE: To investigate the incidence and distribution of lymph node metastasis in patients with different gene mutations among pathological T1 non-small-cell lung cancers (NSCLC). METHODS: NSCLC cases resected in our institution between 2016 and 2018 were included. Driver mutation testing was performed in all resected tumor tissues. These patients were grouped by the type of gene mutations. On the basis of protein that mutant-genes encoded involved in the molecular pathway, the genotypes were further classified into four distinct groups: upstream receptor mutant protein (EGFR, HER2 and MET); downstream regulator mutant protein (KRAS and BRAF); fusion mutant protein (ROS1, ALK and RET) and the wild type group. The incidence of lymph node metastasis was compared among different groups. RESULTS: Of the 1052 patients enrolled, the frequency of positive mutations was 68.0%. The incidence of lymph node metastasis were as follows: wild type (19.3%), ROS1 (72.8%), BRAF (55.5%), ALK (44.7%), HER2 (40%), RET (23.1%), KRAS (15.3%), EGFR (15.3%) and MET mutation (0%) (P < 0.001). The incidence of lymph node metastasis was significantly higher in fusion mutant protein group (45.1%) compared with others (wild type 19.3%, downstream regulator mutant protein 19.1%, upstream receptor mutant protein 15.3%, all P < 0.001). Patients with fusion genes also showed higher proportion of vascular invasion and positive lymph node ratio of greater than 0.33 compared to others. CONCLUSION: Different genotypes of NSCLC have different propensity to develop lymph node metastasis. Cases of fusion gene mutations had a higher risk and burden of lymph node metastasis than other genotypes, which may indicate that more intensive treatment or surveillance strategies should be applied for these patients.
OBJECTIVE: To investigate the incidence and distribution of lymph node metastasis in patients with different gene mutations among pathological T1 non-small-cell lung cancers (NSCLC). METHODS:NSCLC cases resected in our institution between 2016 and 2018 were included. Driver mutation testing was performed in all resected tumor tissues. These patients were grouped by the type of gene mutations. On the basis of protein that mutant-genes encoded involved in the molecular pathway, the genotypes were further classified into four distinct groups: upstream receptor mutant protein (EGFR, HER2 and MET); downstream regulator mutant protein (KRAS and BRAF); fusion mutant protein (ROS1, ALK and RET) and the wild type group. The incidence of lymph node metastasis was compared among different groups. RESULTS: Of the 1052 patients enrolled, the frequency of positive mutations was 68.0%. The incidence of lymph node metastasis were as follows: wild type (19.3%), ROS1 (72.8%), BRAF (55.5%), ALK (44.7%), HER2 (40%), RET (23.1%), KRAS (15.3%), EGFR (15.3%) and MET mutation (0%) (P < 0.001). The incidence of lymph node metastasis was significantly higher in fusion mutant protein group (45.1%) compared with others (wild type 19.3%, downstream regulator mutant protein 19.1%, upstream receptor mutant protein 15.3%, all P < 0.001). Patients with fusion genes also showed higher proportion of vascular invasion and positive lymph node ratio of greater than 0.33 compared to others. CONCLUSION: Different genotypes of NSCLC have different propensity to develop lymph node metastasis. Cases of fusion gene mutations had a higher risk and burden of lymph node metastasis than other genotypes, which may indicate that more intensive treatment or surveillance strategies should be applied for these patients.