FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study.
BACKGROUND
In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials.


METHODS
FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed.


RESULTS
The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (P<0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P=0.0073) and UK (OS: 0.45 vs 1.9 years, P<0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P=0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour.


CONCLUSIONS
A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive.
AstraZeneca Asia & Emerging Markets, Innovative Medicines, Shanghai, China.
X
X
Su
AstraZeneca Asia & Emerging Markets, Innovative Medicines, Shanghai, China.
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P
Zhan
AstraZeneca Asia & Emerging Markets, Innovative Medicines, Shanghai, China.
P R
PR
Gavine
AstraZeneca, Oncology Innovative Medicines, Alderley Park, Macclesfield, UK.
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Morgan
AstraZeneca, Oncology Innovative Medicines, Alderley Park, Macclesfield, UK.
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C
Womack
Department of General Surgery, Renji Hospital, School of Medicine, Jiaotong University, Shanghai, China.
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Ni
Department of General Surgery, Renji Hospital, School of Medicine, Jiaotong University, Shanghai, China.
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D
Shen
1] Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea [2] Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Y-J
YJ
Bang
1] Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea [2] Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
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SA
Im
1] Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea [2] Department of Pathology, Seoul National University Hospital, Seoul, Korea.
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W
Ho Kim
1] Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea [2] Department of Pathology, Seoul National University Hospital, Seoul, Korea.
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EJ
Jung
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
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HI
Grabsch
AstraZeneca, Oncology Innovative Medicines, Alderley Park, Macclesfield, UK.
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E
Kilgour
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002681:China; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D056910:Republic of Korea; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D013534:Survival; D006113:United Kingdom; D055815:Young Adult
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; C508053:ERBB2 protein, human; C496353:FGFR2 protein, human