title: Differential expression ofCRKLandAXLgenes in lung adenocarcinoma subtypes according to the epidermal growth factor receptor and anaplastic lymphoma kinase gene status.
abstract: Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related mortality. Adenocarcinoma (AC) is the predominant histological type of NSCLC; however, AC consists of several subtypes. It has not yet been determined whether there is a correlation of CRKL and AXL expression with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene status in lung AC. We assayed exons 18 through 21 of theEGFRgene by direct sequencing;ALKrearrangement and the expression of CRKL and AXL were detected by immunostaining. A total of 212 cases of AC were included in this study, diagnosed using the novel classification system established by the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society in 2011, including 69 acinar ACs, 17 lepidic predominant ACs (LPAs), 63 papillary, 14 mucinous, 17 micropapillary and 32 solid ACs. Of the 212 cases, 101 harboredEGFRmutations. The most common subtypes carrying delK745-S753 were papillary and acinar ACs.ALKrearrangement was found in 23 cases (11%) of lung ACs. Acinar and solid ACs were the most frequent subtypes withALKaberrance, particularly in acinar ACs with cribriform structure (4/5 cases, 80%). The expression of CRKL was significantly different among the AC subtypes (P=0.01), with the highest and lowest expression levels of CRKL protein in papillary ACs and LPAs, respectively (P<0.05). AXL expression was also significantly different among the AC subtypes (P=0.002) and was correlated with lymph node infiltration in acinar ACs. ACs withEGFRmutations exhibited high levels of AXL protein expression compared to those without mutations (P<0.001). Acinar AC with cribriform structure is a distinct subtype that frequently harborsALKrearrangement. The activation ofAXLmay be one of the factors contributing to the invasion of acinar and micropapillary ACs.
authors.affiliation: Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: DA-Ping
authors.initials: DP
authors.lastname: Yu
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Dong
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing 101149, P.R. China.
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Cai
keywords: AXL; CRKL; anaplastic lymphoma kinase gene rearrangement; epidermal growth factor receptor gene mutation; lung adenocarcinoma