FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis.
BACKGROUND
The amplicon on 8p11.2 is reported to be found in up to 10% of breast carcinomas. It has been demonstrated recently that this amplicon has four separate cores. The second core encompasses important oncogene candidates, including the fibroblast growth factor receptor 1 (FGFR1) gene. Recent studies have demonstrated that specific FGFR1 amplification correlates with gene expression and that FGFR1 activity is required for the survival of a FGFR1 amplified breast cancer cell line.


METHODS
FGFR1 amplification was analysed in tissue microarrays comprising a cohort of 880 unselected breast tumours by means of chromogenic in situ hybridisation using inhouse-generated FGFR1-specific probes. Chromogenic in situ hybridisation signals were counted in a minimum 30 morphologically unequivocal neoplastic cells. Amplification was defined as >5 signals per nucleus in more than 50% of cancer cells or when large gene copy clusters were seen.


RESULTS
FGFR1 amplification was observed in 8.7% of the tumours and was significantly more prevalent in patients >50 years of age and in tumours that lacked HER2 expression. No association was found with other histological parameters. Survival analysis revealed FGFR1 amplification as an independent prognostic factor for overall survival in the whole cohort. Subgroup analysis demonstrated that the independent prognostic impact of FGFR1 amplification was only seen in patients with oestrogen-receptor-positive tumours, where FGFR1 amplification was the strongest independent predictor of poor outcome.


CONCLUSIONS
Given that up to 8.7% of all breast cancers harbour FGFR1 amplification and that this amplification is an independent predictor of overall survival, further studies analysing the FGFR1 as a potential therapeutic target for breast cancer patients are warranted.
Elbauomy Elsheikh
Somaia
S
Department of Histopathology, School of Molecular Medical Sciences, Queen's Medical Centre, Nottingham University Hospitals Trust and University of Nottingham, Nottingham, UK. mrxse@nottingham.ac.uk
Green
Andrew R
AR
Lambros
Maryou B K
MB
Turner
Nicholas C
NC
Grainge
Matthew J
MJ
Powe
Des
D
Ellis
Ian O
IO
Reis-Filho
Jorge S
JS
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis* / Q000235:genetics*
C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1