PMID- 27194548 OWN - NLM STAT- MEDLINE DCOM- 20170216 LR - 20220408 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 469 IP - 2 DP - 2016 Aug TI - Amplification of FGFR1 gene and expression of FGFR1 protein is found in different histological types of lung carcinoma. PG - 173-82 LID - 10.1007/s00428-016-1954-5 [doi] AB - 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. FAU - Sousa, Vitor AU - Sousa V AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. vitorsousa.patol@gmail.com. AD - CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. vitorsousa.patol@gmail.com. AD - Centre of Pulmonology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. vitorsousa.patol@gmail.com. AD - Service of Anatomical Pathology, University Hospital of Coimbra, Coimbra, Portugal. vitorsousa.patol@gmail.com. AD - Vitor Manuel Leitao de Sousa, Instituto de Anatomia Patologica, Faculdade de Medicina, Universidade de Coimbra, 3000-054, Coimbra, Portugal. vitorsousa.patol@gmail.com. FAU - Reis, Diana AU - Reis D AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. FAU - Silva, Maria AU - Silva M AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - Centre of Pulmonology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. FAU - Alarcao, Ana Maria AU - Alarcao AM AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - Centre of Pulmonology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. FAU - Ladeirinha, Ana Filipa AU - Ladeirinha AF AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. FAU - d'Aguiar, Maria Joao AU - d'Aguiar MJ AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. FAU - Ferreira, Teresa AU - Ferreira T AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. FAU - Caramujo-Balseiro, Sandra AU - Caramujo-Balseiro S AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - Polytechnic Institute of Castelo Branco, Superior Health Science School, Castelo Branco, Portugal. FAU - Carvalho, Lina AU - Carvalho L AD - Institute of Anatomical and Molecular Pathology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - CIMAGO-Research Center for Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - Centre of Pulmonology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. AD - Service of Anatomical Pathology, University Hospital of Coimbra, Coimbra, Portugal. LA - eng PT - Journal Article DEP - 20160519 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - EC 2.7.10.1 (FGFR1 protein, human) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) SB - IM MH - Adenocarcinoma/*metabolism/*pathology MH - Adenocarcinoma of Lung MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - Gene Amplification/genetics MH - Gene Dosage/genetics MH - Humans MH - Immunohistochemistry/methods MH - In Situ Hybridization, Fluorescence/methods MH - Lung Neoplasms/*genetics/*metabolism/pathology MH - Male MH - Middle Aged MH - Receptor, Fibroblast Growth Factor, Type 1/*genetics/*metabolism OTO - NOTNLM OT - CK7 OT - FGFR1 OT - Lung carcinomas OT - TTF1 OT - Targeted therapy OT - Vimentin EDAT- 2016/05/20 06:00 MHDA- 2017/02/17 06:00 CRDT- 2016/05/20 06:00 PHST- 2015/05/17 00:00 [received] PHST- 2016/05/05 00:00 [accepted] PHST- 2016/01/01 00:00 [revised] PHST- 2016/05/20 06:00 [entrez] PHST- 2016/05/20 06:00 [pubmed] PHST- 2017/02/17 06:00 [medline] AID - 10.1007/s00428-016-1954-5 [pii] AID - 10.1007/s00428-016-1954-5 [doi] PST - ppublish SO - Virchows Arch. 2016 Aug;469(2):173-82. doi: 10.1007/s00428-016-1954-5. Epub 2016 May 19.