title: Coexpression of receptor tyrosine kinase AXL and EGFR in human primary lung adenocarcinomas.
abstract: AXL has been identified as a tyrosine kinase switch that causes resistance to inhibitors targeting epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer (NSCLC). However, the relationship between 2 receptor tyrosine kinases, AXL and EGFR, and the relevance of AXL expression with EGFR mutation status in treatment-naive human NSCLCs remain uncertain. In this study, we evaluated the coexpression pattern of AXL, EGFR, and pEGFR(1068) in 109 lung adenocarcinoma patients with or without an EGFR mutation. There were 68 (62.4%) patients with tumors harboring EGFR mutations such as 19 del and/or L858R; 2 patients were T790M positive. The expression of AXL, EGFR, and pEGFR(1068) was detected in 60 (55%), 68 (62.4%), and 57 (52.3%) of 109 patients, respectively. The positive rates of EGFR and pEGFR(1068) were associated with the L858R mutation alone or with the 19 del and L858R mutation status. Further analysis indicated that the percentage of AXL(+)/EGFR(+)/pEGFR(1068) coexpression in 68 EGFR-activating mutations patients was significantly higher than that in 39 EGFR wild-type patients (30.9% versus 10.3%, P=.015). Furthermore, in the subgroup of AXL(+) patients (35 mutation(+) and 23 wild-type patients), the coexpression rates of AXL(+)/pEGFR(1068+) and AXL(+)/EGFR(+)/pEGFR(1068+) in patients with EGFR mutations were significantly higher compared with those in wild-type patients (both P<.05). Our study emphasized that the AXL and EGFR receptor tyrosine kinases were coexpressed in a subgroup of treatment-naive lung adenocarcinomas with or without EGFR mutations. Anti-AXL therapeutics delivered up front in combination with an EGFR inhibitor might prevent or delay resistance in patients with AXL-positive, EGFR-mutant, or wild-type NSCLC.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: zhenzhouwu11@163.com.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: 1351800048@qq.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: longfanyh@163.com.
authors.forename: Liyun
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: pangwenshuai0202@163.com.
authors.forename: Wenshuai
authors.initials: W
authors.lastname: Pang
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: 66743941@qq.com.
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Han
authors.affiliation: Department of Pathology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China. Electronic address: sjzwangjuan@126.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, Tumor Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China. Electronic address: yuep111@163.com.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: 240139349@qq.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: huijunduan@126.com.
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address: xinglingxiao@hotmail.com.
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Xing
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: AXL; EGFR inhibitors; EGFR mutation; NSCLC