FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study

X Su, P Zhan, P R Gavine, S Morgan, C Womack, X Ni, D Shen, Y-J Bang, S-A Im, W Ho Kim, E-J Jung, H I Grabsch, E Kilgour, X Su, P Zhan, P R Gavine, S Morgan, C Womack, X Ni, D Shen, Y-J Bang, S-A Im, W Ho Kim, E-J Jung, H I Grabsch, E Kilgour

Abstract

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.

Conclusion: 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.

Figures

Figure 1
Figure 1
Kaplan–Meier OS analysis using FGFR2 FISH score in three separate patient cohorts. Median OS and 95% CI for pairwise comparisons are provided.
Figure 2
Figure 2
Dual-colour FISH shows FGFR2 copy-number normal (A), copy-number increase (B) and amplification (C). Red and green signals highlight FGFR2 gene and centromere 10 probes, respectively. Four-colour FISH reveals distinct tumour regions with either FGFR2 or HER2 amplification (D). Gold and aqua probes highlight HER2 and centromere 17.

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