Preoperative serum carcinoembryonic antigen levels are associated with histologic subtype, EGFR mutations, and ALK fusion in patients with completely resected lung adenocarcinoma

OncoTargets and Therapy Dovepress open access to scientific and medical research Original Research OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Open Access Full Text Article Preoperative serum carcinoembryonic antigen levels are associated with histologic subtype, EGFR mutations, and ALK fusion in patients with completely resected lung adenocarcinoma This article was published in the following Dove Press journal: OncoTargets and Therapy 7 July 2017 Number of times this article has been viewed Zeng Wang 1 Shifeng Yang 2 Hongyang Lu 3,4 Department of Pharmacy, Department of Pathology, 3Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, 4 Department of Oncology, Wenzhou Medical University, Wenzhou, People’s Republic of China 1 2 Background: Serum carcinoembryonic antigen (CEA) is often elevated in lung adenocarcinoma, but not in all patients. Meanwhile, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusion protein are the main driving forces in lung adenocarcinoma. However, whether CEA levels are associated with histologic subtype, EGFR mutations, and ALK fusion remain largely unclear. Methods: Preoperative serum CEA levels, postoperative histologic subtypes, and statuses of EGFR mutations and ALK fusion protein were retrospectively assessed in 442 patients with completely resected lung adenocarcinoma treated from January 2014 to December 2015 at Zhejiang Cancer Hospital, People’s Republic of China. Results: EGFR mutations were found in 69.9% (309/442) of lung adenocarcinoma patients, and ALK fusion protein in 4.5% (20/442). EGFR mutations occurred more frequently in the lepidic subtype (P=0.001). High preoperative serum CEA levels (CEA 20 ng/mL) were independently associated with EGFR mutations (P0.001). Moreover, in patients with CEA levels of 21–49 ng/mL, the EGFR mutation rate was 88.2%, which was higher compared to those obtained in the other subgroups. In addition, all specimens were invasive adenocarcinoma, with lepidic (18.6%), papillary (15.4%), acinar (52.7%), solid (9.7%), micropapillary (3.2%), and mucinous predominant (0.4%) subtypes; CEA levels in patients with the solid subtype were higher than those of other histologic subtypes (P=0.001). Conclusion: Preoperative serum CEA levels can serve as a reference marker to identify the histologic subtype, and EGFR mutation or ALK fusion protein status, in lung adenocarcinoma patients. Moreover, histological subtypes could also predict EGFR mutations. Keywords: lung adenocarcinoma, carcinoembryonic antigen, EGFR, ALK, histologic subtype Introduction Correspondence: Hongyang Lu Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, 1 East Banshan Road, Gongshu District, Hangzhou 310022, People’s Republic of China Tel +86 571 8812 2094 Fax +86 571 8812 2508 Email 3345 submit your manuscript | www.dovepress.com OncoTargets and Therapy 2017:10 3345–3351 Dovepress © 2017 Wang et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/OTT.S134452 Powered by TCPDF (www.tcpdf.org) Lung adenocarcinoma subtypes, including lepidic, papillary, acinar, solid, micropapillary, and mucinous predominant, have been defined by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) international histological classification. Epidermal growth factor receptor (EGFR) mutations easily occur in lung adenocarcinoma patients, especially in females and non-smokers. The rates of EGFR mutations in lung adenocarcinoma in People’s Republic of China are higher than those of Caucasian populations.1–3 EGFRtyrosine kinase inhibitors are considered the first-line therapeutics for lung adenocarcinoma harboring EGFR mutations.4,5 Anaplastic lymphoma kinase (ALK) fusion protein Dovepress OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 37.59.46.207 on 12-Jul-2018 For personal use only. Wang et al is present in about 5% of lung adenocarcinoma cases.6,7 ALK inhibitors are superior to chemotherapy in lung adenocarcinoma patients with ALK rearrangement, improving symptoms and quality of life.8–10 A higher intracranial disease control rate in patients with brain metastasis was also demonstrated for ALK inhibitors compared with chemotherapy.11,12 Both EGFR and ALK are the main driving genes in lung adenocarcinoma. Serum carcinoembryonic antigen (CEA) levels are usually elevated in lung adenocarcinoma patients, constituting an effective and noninvasive method for the diagnosis of this malignancy.13,14 CEA levels are independently associated with EGFR gene mutations, and the frequency of ALK fusion gene among patients with a serum CEA concentration below 5 ng/mL seems to be higher than that of patients with a concentration above 5 ng/mL (P=0.021).15 CEA levels in patients with EGFR mutations and ALK fusion protein might be different from those of cases with no EGFR mutation or ALK fusion protein. As the lung cancer research field is rapidly evolving, molecular pathology attracts increasing attention. Meanwhile, information regarding the clinical characteristics and molecular pathology of lung adenocarcinoma subtypes as defined by the new IASLC/ATS/ERS classification remains limited. There may be also differences in CEA levels among the histologic subtypes of lung adenocarcinoma. This study aimed to further assess the associations of CEA levels with histologic subtype, and the status of EGFR mutations and ALK fusion protein. A total of 442 patients were assessed, and clinicopathological parameters, serum CEA levels, and the status of EGFR mutations and ALK fusion protein were analyzed. Methods Patients and eligibility criteria A total of 442 cases with completely resected lung adenocarcinoma (184 males and 258 females), treated from January 2014 to December 2015 in Zhejiang Cancer Hospital, People’s Republic of China, were retrospectively assessed. Inclusion criteria were stage IA–IIIA completely resected lung adenocarcinoma and 18 years of age or older. Patients were excluded from the study for any of the following reasons: 1) history of other malignancy (unless more than 5 (...truncated)