title: Micropapillary: A component more likely to harbour heterogeneous EGFR mutations in lung adenocarcinomas.
abstract: The micropapillary (MP) subtype has recently been established to be a distinct marker of poor prognosis in lung adenocarcinomas (LACs). According to the 2015 WHO classification system, LAC constituents are required to be precisely reported. T790M mutation and an insertion in exon 20 (E20ins) are associated with EGFR-TKI resistance. A total of 211 LAC patients were involved in this study, and EGFR mutations were determined using an amplification refractory mutation system (ARMS). Sex, smoking history, lymph node status, and clinical stage differed significantly between the EGFR wild type and mutant groups (p < 0.05). The EGFR mutation occurred more frequently in female, non-smokers, ACs with papillary (85.7%) or MP components (91.4%) (p < 0.001). Twenty ACs with naïve T790M or E20ins were microdissected. The AC constituents metastasizing to lymph nodes exhibited a phenotype and EGFR status that was consistent with the primary loci constituents. Glomerulus-like solid components exhibited the same EGFR status as the surrounding T790M-mutated MP components. The MP and glomerulus-like portions in AC tumours exhibited a congenial EGFR status, but the acinar cells with papillary cells were heterogeneous. The naïve T790M mutants, although minor in the MP component, dramatically increased after EGFR-TKI therapy and indicate that the MP components feature intrinsic heterogeneity.
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, Beijing, 101149, P.R. China.
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Cai
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, Beijing, 101149, P.R. China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Dong
authors.affiliation: Department of Medical Oncology, 1st Division, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, Beijing, 101149, P.R. China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Wu
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, Beijing, 101149, P.R. China.
authors.forename: Zi-Chen
authors.initials: ZC
authors.lastname: Liu
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, 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 Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, 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 Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, Beijing, 101149, P.R. China.
authors.forename: Xue-Jing
authors.initials: XJ
authors.lastname: Chen
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, Beijing, 101149, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, 97 Beiguan Machang Rd, Tongzhou District, Beijing, 101149, P.R. China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Zhao
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D010641:Phenotype; D011379:Prognosis; D013696:Temperature
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors