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

• Published in: PloS one 2022-02, Vol.17 (2), p.e0264011-e0264011
• Main Authors: Schrumpf, Thorben, Behrens, Hans-Michael, Haag, Jochen, Krüger, Sandra, Röcken, Christoph
• Format: Article
• Language: English
• Subjects: Amplification; Antigens; Biology and Life Sciences; Cancer; Cancer therapies; Chemotherapy; Cohort Studies; Engineering and Technology; Female; Fibroblast growth factor receptor 2; Gastric cancer; Gastrointestinal cancer; Gastrointestinal surgery; Gene Amplification; Gene Expression Regulation, Neoplastic; Genetic aspects; Growth factor receptors; Growth factors; Health aspects; Heterogeneity; Histology; Humans; Hybridization; Immunohistochemistry; In Situ Hybridization; Kaplan-Meier Estimate; Localization; Lymphatic system; Male; Medical prognosis; Medicine and Health Sciences; Metastasis; Neoplasm Grading; Pathology; Patient outcomes; Patients; Phenotypes; Protein expression; Proteins; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptor, Fibroblast Growth Factor, Type 2 - metabolism; Research and Analysis Methods; Staining; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Survival; Survival Analysis; Tumors; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0264011

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).