Gene status and clinicopathologic characteristics of lung adenocarcinomas with mediastinal lymph node metastasis.

Shumeng Zhang,Jing Zheng,Jianying Zhou,Bing Yan,Jing Zhao

doi:10.18632/oncotarget.11494

Abstract

Lung cancer with mediastinal lymph node metastasis is more likely to develop recurrence and metastasis after complete resection and targeted therapy is a promising treatment strategy. We performed amplification refractory mutation system (ARMS) fluorescence quantitative PCR to detect the gene status of EGFR, ALK, ROS1 and RET in resected samples from 280 patients who were confirmed to have primary lung adenocarcinomas with N1-N2 lymph node metastasis. Of the 280 patients enrolled, the frequency of EGFR mutations, ALK fusions, ROS1 fusions, RET fusions and no mutations was 42.9%, 10.7%, 1.8%, 3.6% and 42.9%, respectively. Five patients exhibited the coexistence of the EGFR and ALK alterations. ALK, ROS1 and RET fusions were mutually exclusive. The frequency of EGFR mutation was significantly lower among patients with poor differentiation, while the rates of ALK and ROS1 fusions were the opposite. RET fusions also tended to be more prevalent in poorly differentiated patients. EGFR and ALK double positive tumors were characterized by significantly smaller size compared with those had single gene alteration. Our study comprehensively analyzed the distinct and common clinicopathologic characteristics according to genotypes of the cohort, which should help in categorizing patients for efficient screening.

Highlights

Diagnosis at an early stage is increasing and therapeutic methodology is progressing, lung cancer remains the leading cause of cancer-related deaths worldwide [1]
We identified that the frequencies of EGFR, anaplastic lymphoma kinase (ALK), RET and ROS1 were 42.9%, 10.7%, 3.6% and 1.8%, respectively
We found that the incidence of EGFR mutations was associated with female sex in univariate analysis instead of multivariate analysis, which was in concordance with previous studies [11]

Summary

Introduction

Diagnosis at an early stage is increasing and therapeutic methodology is progressing, lung cancer remains the leading cause of cancer-related deaths worldwide [1]. Crizotinib, the ALK/MET TKI, has shown dramatic therapeutic effects against lung cancer with anaplastic lymphoma kinase (ALK) rearrangements. ROS1 and RET fusions have attracted much attention, as they were both identified in approximately 1%-2% of patients with NSCLC. Clinical trials are underway to investigate the therapeutic effects of cabozantinib and vandetanib against NSCLC harboring RET fusions [3]. All of these achievements highlight the importance of matching targeted therapy to the genetically defined subgroups of patients. This may be due to the different nature of the study cohorts, as many of the cohorts are unselected NSCLCs or adenocarcinomas. Comprehensive studies of alteration-specific and common clinicopathologic features are rare [4]

Methods

Results

Conclusion