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

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

Jinghan Shi #  1 , Weiqing Gu #  2 , Yanfeng Zhao  1 , Junjie Zhu  1 , Gening Jiang  1 , Minwei Bao  1 , Jingyun Shi  3
Affiliations

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

Jinghan Shi et al. Cancer Manag Res. .

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, Ptrend =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.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flow diagram for this study. Abbreviations: EML4, echinoderm microtubule-associated protein-like 4; ALK, anaplastic lymphoma kinase; TKI, tyrosine kinase inhibitors.
Figure 2
Figure 2
Disease-free survival curve analyses for surgically resected adenocarcinoma after propensity score matching, stratified by detection for EML4-ALK fusion gene. Notes: (A) DFS curves in all patients. (B) DFS curves in female patients. (C) DFS curves in male patientsAbbreviations: EML4, echinoderm microtubule-associated protein-like 4; ALK, anaplastic lymphoma kinase.
See this image and copyright information in PMC

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