title: Amplification of FGFR1 gene and expression of FGFR1 protein is found in different histological types of lung carcinoma.
abstract: Although lung cancer continues to be the leading cause of cancer-related death, accurate diagnosis followed by personalized treatment is expected to raise the 5-year survival rate. Targeted therapies are now in routine clinical use, in particular for lung adenocarcinoma (ADC). Fibroblast growth factor receptor 1 (FGFR1) has recently emerged as a molecular target, especially in squamous cell/epidermoid carcinoma (SQC) of the lung. This paper evaluates FGFR1 expression and gene copy number in adenocarcinomas, squamous cell carcinomas, pleomorphic carcinomas (PLEOMC) and adenosquamous carcinomas (ADSQC) of the lung and also explores the epithelial-mesenchymal transition (EMT) pathway. We studied 76 lung carcinomas: 34 ADC, 24 SQC, 10 PLEOMC and 8 ADSQC. FGFR1 expression was evaluated by immunohistochemistry and gene amplification by fluorescence in situ hybridization (FISH). Higher FGFR1 protein expression was observed in all tumour types compared to non-tumour tissue. FGFR1 expression was higher in ADC and PLEOMC than in SQC. We found a tendency to higher expression in ADC than in SQC and significantly higher expression in PLEOMC than in other histological subtypes. FISH-based amplification of FGFR1 was identified in 15 (20 %) lung carcinomas: 5 (15 %) ADC, 5 (21 %) SQC, 3 (30 %) PLEOMC and 2 (25 %) ADSQC. Amplification was more frequent in SQC without significant differences. FGFR1 protein is expressed in the majority of lung carcinomas, though it is higher in ADC and PLEOMC (the latter may reflect the importance of FGFR1 control of the EMT pathway). FGFR1 amplification was identified in all types of lung carcinoma. Although FGFR1 is most frequently amplified in SQC, other histological types merit assessment of FGFR1 amplification, in order to select patients that might benefit from targeted therapy.
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. vitorsousa.patol@gmail.com.|CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. vitorsousa.patol@gmail.com.|Centre of Pulmonology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. vitorsousa.patol@gmail.com.|Service of Anatomical Pathology, University Hospital of Coimbra, Coimbra, Portugal. vitorsousa.patol@gmail.com.|Vitor Manuel Leitão de Sousa, Instituto de Anatomia Patológica, Faculdade de Medicina, Universidade de Coimbra, 3000-054, Coimbra, Portugal. vitorsousa.patol@gmail.com.
authors.forename: Vitor
authors.initials: V
authors.lastname: Sousa
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Reis
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|Centre of Pulmonology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: Silva
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|Centre of Pulmonology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Alarcão
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Filipa
authors.initials: AF
authors.lastname: Ladeirinha
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: d'Aguiar
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Ferreira
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|Polytechnic Institute of Castelo Branco, Superior Health Science School, Castelo Branco, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Caramujo-Balseiro
authors.affiliation: Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|Centre of Pulmonology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|Service of Anatomical Pathology, University Hospital of Coimbra, Coimbra, Portugal.
authors.forename: Lina
authors.initials: L
authors.lastname: Carvalho
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: CK7; FGFR1; Lung carcinomas; TTF1; Targeted therapy; Vimentin