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E-Poster Display

1409P - Comparing different methods of FGFR1 aberrations analysis in squamous cell lung cancer (SqCLC) targeted therapy

Date

17 Sep 2020

Session

E-Poster Display

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Monika Skupinska

Citation

Annals of Oncology (2020) 31 (suppl_4): S754-S840. 10.1016/annonc/annonc283

Authors

M.M. Skupinska1, T. Obtulowicz1, J. Moes-Sosnowska2, A. Rozy2, E. Szczepulska3, R. Langfort3, J. Chorostowska Wynimko4, A. Stanczak1, J. Pieczykolan1, M. Wieczorek1, D. Popiel1

Author affiliations

  • 1 Research And Development Centre, Celon Pharma S.A., 05-092 - Kielpin-Lomianki/PL
  • 2 Department Of Genetics And Clinical Immunology, National Institute of Tuberculosis and Lung Diseases,, Warsaw/PL
  • 3 Departament Of Pathology, National Institute of Tuberculosis and Lung Diseases,, Warsaw/PL
  • 4 Department Of Genetics And Clinical Immunology, National Institute of Tuberculosis and Lung Diseases,, 02-676 - Warsaw/PL

Resources

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Abstract 1409P

Background

Data indicate that aberrations in fibroblast growth factor receptor 1 (FGFR1) e.g. gene amplification, fusions or mutations are involved in pathogenesis of SqCLC. Correlation between FGFR1 aberrations and response to treatment was observed in several clinical trials of FGFR inhibitors. In targeted therapies, choosing the best patient selection method is crucial for maximum therapeutic response. Here we compare different methods of FGFR1 aberrations analysis.

Methods

20 formalin-fixed, paraffin embedded (FFPE) samples with the highest tumour density were selected from cohort of 204 patients with SqCLC. FGFR1 aberrations were analysed using: -NanoString platform: level of FGFR1 gene mRNA and copy number variation (CNV) were determined using custom panels. Ratio ≥ 4 was considered elevated, compared to neoplastically unchanged lung tissue. mRNA level ≥ 800 counts was considered elevated. RT-PCR was used to confirm gene expression, - fluorescence in situ hybridization (FISH) was performed to assess CNV. Amplification criteria were previously described by Schultheis et al., - immunohistochemistry (IHC) was used for FGFR1 expression analysis. Overexpression was defined as staining intensity 2 or 3+ (graded from 0 to 3+) in >10% of the cancer cells. Spearman test was performed to assess correlation.

Results

The range of mRNA level was between 289.05 and 8902.82 counts (mean=1667.85). FGFR1 amplification determined by FISH was observed in 11/20 (55%) samples. Overexpression of FGFR1 protein was observed in 10/20 (50%) specimens. FISH and CNV NanoString results were consistent in 75% of SqCLC samples (15/20). High-level amplification evaluated by FISH correlated with CNV assessed with NanoString (p=0.0154; r=0.5) for 20 SqCLC tumour samples. mRNA (NanoString) and protein overexpression level for FGFR1 were consistent in 18/19 (94.70%) and correlated (p<0.0001; r=0.9) for 19 SqCLC tumour samples.

Conclusions

Multiplexed analysis of FGFR1 aberrations may contribute to broader patient population eligible for FGFR inhibitor therapy, which may increase its overall clinical feasibility and potential therapeutic benefits.

Clinical trial identification

Editorial acknowledgement

The research was co-financed by the National Center of Research and Development and Celon Pharma S.A., project "CELONKO", grant number STRATEGMED2/266776/17/NCBR/2015.

Legal entity responsible for the study

Celon Pharma S.A.

Funding

Celon Pharma S.A. & NCBR grant.

Disclosure

All authors have declared no conflicts of interest.

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