The clinicopathological and molecular characteristics of resected EGFR‐mutant lung adenocarcinoma

Abstract

Background Epidermal growth factor receptor (EGFR) mutations were frequently found with concomitant genetic alterations in lung adenocarcinoma (LUAD). This study aimed to investigate the profile of concomitant alterations of EGFR‐mutant LUAD ≤3 cm in size and its prognostic effect on recurrence. Methods From January 2018 to December 2018, patients with resected LUAD ≤3 cm in size in Shanghai Chest Hospital were identified. All patients underwent capture‐based targeted next‐generation sequencing (NGS) with a panel of 68 lung cancer‐related genes and were found with EGFR mutation. Clinicopathological and molecular characteristics and recurrence‐free survival (RFS) were analyzed. Results A total of 637 patients were enrolled in this study. The top three frequent co‐mutational genes were TP53 (179 of 637, 28.1%), PIK3CA (27 of 637, 4.2%), and ATM (22 of 637, 3.5%). The most common amplified genes were EGFR (37 of 637, 5.8%), followed by CDK4 (37 of 637, 5.8%) and MYC (12 of 637, 2.0%). Only TP53 mutation and EGFR amplification were adverse prognostic factors for RFS (all p < 0.001) in univariate analysis. Multivariable analysis further demonstrated that TP53 mutation and EGFR amplification were independent risk factors for RFS [(hazard ratio (HR) 2.07, 95% confidence interval (CI) 1.07–4.00, p = 0.030; HR 3.09, 95% CI 1.49–6.40, p = 0.002, respectively]. Conclusions Concomitant TP53 mutation and EGFR amplification were poor prognostic factors for RFS in patients with EGFR‐mutant resected LUAD. Our findings provide valuable understanding of the impact of concurrent alterations and implication for better implementation of precision therapy for patients.

Prognosis of recurrence after complete resection in early-stage lung adenocarcinoma based on molecular alterations: a systematic review and meta-analysis

“…Following a review of the titles and abstracts, a total of 100 articles related to molecular alterations were carefully chosen by reading the entire text. The prognosis data related to TP53 13 , 14 , BRAF 15 , 16 , HER2 16 and ALK rearrangement 17 were excluded due to a limited number of studies. Finally, 18 studies were included in the final meta-analyses, which studied EGFR in 11 articles, and KRAS in 9 articles.…”

“…Overall, the clinical studies varied in the methodology for detecting molecular alterations as shown in Table 1 . Seven studies used the polymerase chain reaction (PCR) to examine EGFR 18 – 21 or KRAS alterations 22 – 24 as a marker of disease-free survival; while five studies used the next-generation sequencing (NGS) to detect EGFR 13 , 14 , 16 and KRAS 14 , 16 , 25 alterations. Multiple detection methods were adopted to verify the molecular alterations by six teams of researchers 15 , 26 – 29 .…”

Different prognostic role of EGFR mutation according to the IASLC histological grade in patients with resected early‐stage lung adenocarcinoma

“…However, the mechanism of the adverse prognostic effect of EGFR mutation is largely unexplored. Recent genomic data suggest that EGFR ‐mutant tumours with a poorly differentiated histology show concurrent mutations such as TP53 18,19 . Considering the unfavourable prognosis of concurrent mutations, further studies would be necessary to determine whether TP53 mutations have prognostic significance independent of histological grading.…”

“…Recent genomic data suggest that EGFR-mutant tumours with a poorly differentiated histology show concurrent mutations such as TP53. 18,19 Considering the unfavourable prognosis of concurrent mutations, further studies would be necessary to determine whether TP53 mutations have prognostic significance independent of histological grading. Furthermore, EGFRmutant tumours are typified by the immune evasive microenvironment, which may also affect the prognosis.…”

Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives

“…Evidence from CIT trials, CheckMate 816 and IMpower010, demonstrates that not all patients respond to neoadjuvant or adjuvant CIT and there is a need to test patients for PD-L1 expression and oncogenic driver mutations, and additional prognostic factors such as co-mutations, to identify those most likely to benefit from CIT or TT. 30 , 32 , 60 This emphasizes the need for comprehensive molecular testing with NGS to guide treatment options in the resectable NSCLC setting.…”