Abstract

Whether mutation is associated with lymph node metastases remains unknown. We aim 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). 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. Of the 1,052 patients enrolled, the frequency of positive mutations was 68.0%. The incidence of lymph node metastasis were as follows (Figure 1): wild type (19.3%), ROS1 (72.8%), BRAF (55.5%), ALK (44.7%), HER2 (40%), RET rearrangement (23.1%), KRAS mutation (15.3%), EGFR (15.3%) and MET mutation (0%) (Chi2=43.45, 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 signaling regulator protein 19.1%, upstream signaling receptor protein 15.3%, all P<0.001). Patients with fusion genes showed higher proportion of vascular invasion and positive lymph node ratio of greater than 0.33 compared to other (all P<0.005). In subgroup based on gender, age and smoking history, fusion mutant group was still observed with the highest proportion of node metastasis. 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.

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