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Gastric Cancer
Published in: Gastric Cancer 3/2018

Open Access 01-05-2018 | Original Article

In situ analysis of FGFR2 mRNA and comparison with FGFR2 gene copy number by dual-color in situ hybridization in a large cohort of gastric cancer patients

Authors: Yasutoshi Kuboki, Christoph A. Schatz, Karl Koechert, Sabine Schubert, Janine Feng, Sabine Wittemer-Rump, Karl Ziegelbauer, Thomas Krahn, Akiko Kawano Nagatsuma, Atsushi Ochiai

Published in: Gastric Cancer | Issue 3/2018

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Abstract

Background

Fibroblast growth factor receptor (FGFR2) has been proposed as a target in gastric cancer. However, appropriate methods to select patients for anti-FGFR2 therapies have not yet been established.

Methods

We used in situ techniques to investigate FGFR2 mRNA expression and gene amplification in a large cohort of 1036 Japanese gastric cancer patients. FGFR2 mRNA expression was determined by RNAscope. FGFR2 gene amplification was determined by dual-color in situ hybridization (DISH).

Results

We successfully analyzed 578 and 718 samples by DISH and RNAscope, respectively; 2% (12/578) showed strong FGFR2 gene amplification (FGFR2:CEN10 >10); moderate FGFR2 gene amplification (FGFR2:CEN10 <10; ≥2) was detected in 8% (47/578); and high FGFR2 mRNA expression of score 4 (>10 dots/cell and >10% of positive cells with dot clusters under a 20× objective) was seen in 4% (29/718). For 468 samples, both mRNA and DISH data were available. FGFR2 mRNA expression levels were associated with gene amplification; FGFR2 mRNA levels were highest in the highly amplified samples (n = 12). All highly amplified samples showed very strong FGFR2 mRNA expression (dense clusters of the signal visible under a 1× objective). Patients with very strong FGFR2 mRNA expression showed more homogeneous FGFR2 mRNA expression compared to patients with lower FGFGR2 mRNA expression. Gastric cancer patients with tumors that had an FGFR2 mRNA expression score of 4 had shorter RFS compared with score 0–3 patients.

Conclusion

RNAscope and DISH are suitable methods to evaluate FGFR2 status in gastric cancer. Formalin-fixed paraffin-embedded (FFPE) tissue slides allowed evaluation of the intratumor heterogeneity of these FGFR2 biomarkers.
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Metadata
Title
In situ analysis of FGFR2 mRNA and comparison with FGFR2 gene copy number by dual-color in situ hybridization in a large cohort of gastric cancer patients
Authors
Yasutoshi Kuboki
Christoph A. Schatz
Karl Koechert
Sabine Schubert
Janine Feng
Sabine Wittemer-Rump
Karl Ziegelbauer
Thomas Krahn
Akiko Kawano Nagatsuma
Atsushi Ochiai
Publication date
01-05-2018
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 3/2018
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-017-0758-x

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