FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort.

The significance of fibroblast growth factor receptor 2 (FGFR2) in gastric cancer (GC) has been studied predominantly in Asian patient cohorts. Data on White patients are scarce. Here, we aimed to independently validate the expression and putative tumor biological significance of FGFR2 in a large no...

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Main Authors: Thorben Schrumpf, Hans-Michael Behrens, Jochen Haag, Sandra Krüger, Christoph Röcken
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0264011
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author Thorben Schrumpf
Hans-Michael Behrens
Jochen Haag
Sandra Krüger
Christoph Röcken
author_facet Thorben Schrumpf
Hans-Michael Behrens
Jochen Haag
Sandra Krüger
Christoph Röcken
author_sort Thorben Schrumpf
collection DOAJ
description The significance of fibroblast growth factor receptor 2 (FGFR2) in gastric cancer (GC) has been studied predominantly in Asian patient cohorts. Data on White patients are scarce. Here, we aimed to independently validate the expression and putative tumor biological significance of FGFR2 in a large non-Asian GC cohort. Immunohistochemistry (IHC) was performed on large-area tissue sections from 493 patients with GC and evaluated using the HScore. GCs with moderate and strong FGFR2 expression were studied for Fgfr2 amplification using chromogenic in situ hybridization (CISH). Median overall survival was determined using the Kaplan-Meier method. The majority [240 (99.1%)] of FGFR2-positive GCs showed a variable combination of staining intensities with marked intratumoral heterogeneity, including weak [198 (40.2%) cases], moderate [145 (29.4%)], and strong [108 (21.9%)] staining in diverse combinations. 250 (50.9%) GCs expressed no FGFR2. Fgfr2 gene amplification was found in 40% of selected cases with high protein expression and was also heterogeneous at the cell level. FGFR2 protein expression did not correlate with patient survival in the entire cohort However, using different cutoff values, a negative correlation between FGFR2-expression and patient outcome was found for diffuse-type GC. FGFR2 expression was associated with a lower tumor grade and intestinal phenotype (p≤0.0001). FGFR2-positive diffuse-type GCs classify a small subset of patients with a poor tumor specific survival (5.29±1.3 vs. 14.67±1.9 months; p = 0.004).
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spelling doaj.art-129ca5ac78af448e8581393de1ab59642022-12-21T19:29:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01172e026401110.1371/journal.pone.0264011FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort.Thorben SchrumpfHans-Michael BehrensJochen HaagSandra KrügerChristoph RöckenThe significance of fibroblast growth factor receptor 2 (FGFR2) in gastric cancer (GC) has been studied predominantly in Asian patient cohorts. Data on White patients are scarce. Here, we aimed to independently validate the expression and putative tumor biological significance of FGFR2 in a large non-Asian GC cohort. Immunohistochemistry (IHC) was performed on large-area tissue sections from 493 patients with GC and evaluated using the HScore. GCs with moderate and strong FGFR2 expression were studied for Fgfr2 amplification using chromogenic in situ hybridization (CISH). Median overall survival was determined using the Kaplan-Meier method. The majority [240 (99.1%)] of FGFR2-positive GCs showed a variable combination of staining intensities with marked intratumoral heterogeneity, including weak [198 (40.2%) cases], moderate [145 (29.4%)], and strong [108 (21.9%)] staining in diverse combinations. 250 (50.9%) GCs expressed no FGFR2. Fgfr2 gene amplification was found in 40% of selected cases with high protein expression and was also heterogeneous at the cell level. FGFR2 protein expression did not correlate with patient survival in the entire cohort However, using different cutoff values, a negative correlation between FGFR2-expression and patient outcome was found for diffuse-type GC. FGFR2 expression was associated with a lower tumor grade and intestinal phenotype (p≤0.0001). FGFR2-positive diffuse-type GCs classify a small subset of patients with a poor tumor specific survival (5.29±1.3 vs. 14.67±1.9 months; p = 0.004).https://doi.org/10.1371/journal.pone.0264011
spellingShingle Thorben Schrumpf
Hans-Michael Behrens
Jochen Haag
Sandra Krüger
Christoph Röcken
FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort.
PLoS ONE
title FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort.
title_full FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort.
title_fullStr FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort.
title_full_unstemmed FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort.
title_short FGFR2 overexpression and compromised survival in diffuse-type gastric cancer in a large central European cohort.
title_sort fgfr2 overexpression and compromised survival in diffuse type gastric cancer in a large central european cohort
url https://doi.org/10.1371/journal.pone.0264011
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