FGFR1 expression and gene copy numbers in human lung cancer.
FGFR1 is a receptor tyrosine kinase of which the ligands belong to the fibroblast growth factor family. To evaluate the significance of FGFR1 in lung cancer, we analysed tumours by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Tissue microarrays were constructed containing 380 lung cancer samples including squamous cell carcinomas (SCC), adenocarcinomas (ADC), non-small cell lung cancer not otherwise specified, metastases, neuroendocrine tumours, large cell lung cancer and small cell lung cancer. FGFR1 expression was analysed by IHC and scored semi-quantitatively by a four-tier approach (0, 1, 2, 3). Using dual-colour interphase FISH with probes specific for the locus on 8p12 and the centromere of chromosome 8 (CEN8), copy numbers of FGFR1 were determined. High expression of FGFR1 was associated with increased FGFR1 gene copy numbers in squamous cell carcinoma (p < 0.001). The FGFR1 locus was equally affected by copy number losses and gains. The higher FGFR1 gene copy numbers in SCC compared to ADC did not reach statistical significance. High copy number amplification of FGFR1 was a very rare event, the FGFR1/CEN8 signal ratio reaching a maximum value of 2.75. There were no significant associations between FGFR1 and clinicopathological parameters. Fibroblast growth factor signalling represents an interesting therapeutic target in lung cancer. However, the pathways are complex with potential oncogenic and anti-oncogenic activities. Our data may help to define criteria for selecting patients that may benefit from these new therapeutic options.
Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Ziegelmuehlenweg 1, 07740 Jena, Germany.
Lukas H
LH
Kohler
Masoud
M
Mireskandari
Thomas
T
Knösel
Annelore
A
Altendorf-Hofmann
Almut
A
Kunze
Andreas
A
Schmidt
Norbert
N
Presselt
Yuan
Y
Chen
Iver
I
Petersen
D000368:Aged; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis* / Q000235:genetics*; D046888:Tissue Array Analysis
C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1