Serum carcinoembryonic antigen levels before initial treatment are associated with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.

Wen-Tao Wang,Yin Li,Xiao-Bing Chen,Jie Ma,Jian-Jun Qin

doi:10.7314/apjcp.2014.15.9.3927

Abstract

Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5 ng/ml seemed to be higher than patients with a concentration over 5 ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

Highlights

Lung cancer is the most common cause of cancerrelated deaths, where it is associated with a 5-year worldwide survival rate of less than 15% (Jemal et al, 2011)
Epidermal growth factor receptor (EGFR) mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004)
The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or et al microtubule-associated protein like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene presence in lung adenocarcinoma patients

Summary

Introduction

Lung cancer is the most common cause of cancerrelated deaths, where it is associated with a 5-year worldwide survival rate of less than 15% (Jemal et al, 2011). Epidermal growth factor receptor (EGFR) gene mutations and EML4-ALK fusion gene have been discovered in a subset of NSCLC, especially among patients with pulmonary adenocarcinomas (Soda et al, 2007; Yatabe et al, 2007). The abnormal serum CEA level at diagnosis was a good prognostic factor for TKIs treatment in lung cancer patients (Okamoto et al, 2005). It was surprising, and correlation between EGFR mutations and serum tumor markers in lung adenocarcinoma patients may exist. We retrospectively investigated the correlation between the presence of EGFR gene mutations or ALK gene rearrangement and clinical features, including the serum tumor marker levels, in lung adenocarcinoma patients. Prognostic value of EGFR gene mutations and ALK gene rearrangement was evaluated

Materials and Methods

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Discussion