A comprehensive study on the oncogenic mutation and molecular pathology in Chinese lung adenocarcinoma patients

Abstract

Background: Several genetic driver alterations have been identified in micropapillary lung adenocarcinoma (MPA). However, the frequency of co-alteration of ROS1, EGFR, and EML4-ALK is yet unclear. Herein, we investigated the relationship between clinicopathologic characteristics and well-identified driver mutations of MPA compared with non-micropapillary lung adenocarcinoma (LA). Methods: Formalin-fixed paraffin-embedded (FFPE) sections derived from lung adenocarcinoma patients who never received adjuvant chemotherapy or radiation therapy prior to surgical resection were collected from October 2016 to June 2019. EGFR mutations, ROS1 rearrangements, and EML4-ALK fusion were identified in a set of 131 MPA and LA cases by using the amplification refractory mutation system (ARMS). The response rate and duration of response were assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: EGFR mutations had occurred in 42 (76.4%) MPA patients and 42 (55.3%) LA patients. Interestingly, ROS1 rearrangements were highly enriched only in the MPA cases (6/55, 10.9%) but rarely in the LA cases (1/76, 1.3%). Furthermore, 7.3% (4/55) MPA samples had double gene mutations, while only 1.3% (1/76) LA cases had double gene alterations. Of 5 patients with harboring two driver oncogene mutations, four patients (80%) obtained partial response, and one patient (20%) suffered recurrence. Conclusions: A higher prevalence of ROS1 rearrangement or combined mutations of ROS1, EGFR, and EML4-ALK may play a critical role in the tumorigenesis of MPA. These findings provide a novel therapeutic strategy for patients with malignant MPA through combining TKIs than one TKI.

Analysis of EGFR, KRAS, and PIK3CA gene mutation rates and clinical distribution in patients with different types of lung cancer

“…With the rapid advances in modern molecular biology technology, the treatment model for lung cancer has focused on targeting abnormal molecules in specific signaling pathways [ 5 , 6 ]. In the past 10 years, tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR) have demonstrated remarkable clinical effects and paved the way for effective treatment of lung cancer [ 7 – 9 ]. Indeed, a recent phase III clinical trial (ADAURA [NCT02511106]) assessed the efficacy and safety of a 3rd-generation EGFR-TKI, osimertinib, which had superior efficacy when compared to EGFR-TKI (gefitinib/erlotinib) in treatment-naïve patients with EGFR-mutated advanced NSCLC [ 10 ].…”

Clinical significance of TMEM229A Q200del mutation in lung adenocarcinoma

“…In addition, our previous study demonstrated that micropapillary lung adenocarcinoma had a signi cantly higher tumor mutation burden, such as EGFR mutations, ROS1 fusions. And the incidence of coexisting between EGFR mutations and ROS1 fusions was higher than that other lung adenocarcinoma subtypes [14]. Warth [15] et al also found that patients with micropapillary structure had a signi cantly higher prevalence of driver genetic alterations and rearrangements of ROS1 or ALK than that other histological lung adenocarcinoma subtypes.…”

Epidermal growth factor receptor inhibitors as adjuvant treatment for patients with resected non-small cell lung cancer harboring EGFR mutation: a meta-analysis of randomized controlled clinical trials

“…EGFR mutations were identified in 40–60% of lung adenocarcinomas in East Asians, and exon19 and exon 21 accounted for 87% [ 5 , 6 ]. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of advanced NSCLC, leading to the investigation of adjuvant EGFR-TKI treatment for early-stage disease.…”