Clinicopathological and Prognostic Significance of EML4-ALK Rearrangement in Patients with Surgically Resected Lung Adenocarcinoma: A Propensity Score Matching Study

Jinghan Shi; Weiqing Gu; Yanfeng Zhao; Junjie Zhu; Gening Jiang; Minwei Bao; Jingyun Shi

doi:10.2147/CMAR.S229217

Clinicopathological and Prognostic Significance of EML4-ALK Rearrangement in Patients with Surgically Resected Lung Adenocarcinoma: A Propensity Score Matching Study

Cancer Manag Res. 2020 Jan 24:12:589-598. doi: 10.2147/CMAR.S229217. eCollection 2020.

Authors

Jinghan Shi^#¹, Weiqing Gu^#², Yanfeng Zhao¹, Junjie Zhu¹, Gening Jiang¹, Minwei Bao¹, Jingyun Shi³

Affiliations

¹ Department of Thoracic Surgery, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, People's Republic of China.
² Department of Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, People's Republic of China.
³ Department of Radiology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai, People's Republic of China.

^# Contributed equally.

Abstract

Objective: The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is a key oncogenic driver in non-small cell lung cancer (NSCLC). This study analyzed the clinicopathological characteristics and prognostic significance of EML4-ALK fusion gene in patients with surgically resected adenocarcinoma.

Methods: The clinicopathological characteristics of 1056 consecutive patients with surgically resected stage I-IIIA adenocarcinoma were collected from February 2014 to October 2014, and EML4-ALK rearrangement was detected using real-time polymerase chain reaction (RT-PCR) technology. To compare the imaging and pathological features, a propensity score matching (PSM) method was performed. The follow-up information was collected to evaluate the long-term outcomes of patients with EML4-ALK rearrangement.

Results: The prevalence of EML4-ALK rearrangement was 6.6% in 1056 consecutive patients. A total of 70 EML4-ALK-positive and 210 EML4-ALK-negative patients were identified after PSM. Imaging and pathological analyses showed that EML4-ALK rearrangement was significantly associated with less ground-glass opacity (GGO) (adjusted OR=1.38, 95% CI=1.03-1.85, P_trend =0.029) and higher prevalence of non-invasive mucinous adenocarcinoma mucin-laden adenocarcinomas (non-IMA MLA, adjusted OR=6.79, 95% CI=2.69-17.17, P<0.001). EML4-ALK rearrangement was found to be an unfavorable prognostic factor for disease-free survival (DFS) in female patients (HR=2.26, 95% CI=1.13-4.53, P=0.021).

Conclusion: Our results suggest that adenocarcinomas harboring EML4-ALK fusion gene exhibit specific radiological and pathological characteristics compared with EML4-ALK-negative adenocarcinomas. In female patients, EML4-ALK rearrangement was associated with shorter DFS.

Keywords: NSCLC; adenocarcinoma; anaplastic lymphoma kinase; non-small cell lung cancer; survival.