Evaluation of Fibroblast Growth Factor Receptor 2 Expression, Heterogeneity and Clinical Significance in Gastric Cancer

Abstract

Background: We aimed to evaluate the protein and mRNA expression of fibroblast growth factor receptor 2 (FGFR2) by immunohistochemistry (IHC) and mRNA in situ hybridization (ISH), respectively, and to assess the heterogeneity of FGFR2 expression in gastric cancer (GC). Methods: A tissue microarray containing 362 surgically resected GC tissues and 135 matched metastatic lymph nodes was evaluated using FGFR2b IHC and FGFR2 ISH. FGFR2 fluorescence ISH was also performed in 188 cases. Results: All FGFR2-amplified cases (5 of 188) showed FGFR2b protein and FGFR2 mRNA overexpression (p < 0.001), and FGFR2 amplification was not identified in FGFR2b IHC- and FGFR2 mRNA ISH-negative cases. Kaplan-Meier survival analysis revealed that FGFR2b protein and FGFR2 mRNA overexpression was significantly associated with a poor overall survival (p < 0.001 and p = 0.012, respectively), and multivariate analyses showed that FGFR2 mRNA overexpression was an independent biomarker of a poor overall survival. Intratumoral heterogeneity of FGFR2b protein and FGFR2 mRNA overexpression was observed in 5 of 9 (55.5%) and 18 of 21 (85.7%) cases, respectively. Discordant FGFR2b and FGFR2 expression results between primary and matched metastatic lymph nodes were observed in 5 of 9 (55.5%) and 4 of 14 (28.6%) cases, respectively. Conclusions: Intratumoral heterogeneity and discordant FGFR2b expression in primary tumors and metastatic lymph nodes are common in GC.

Integrated Analysis of Structural Variation and RNA Expression of FGFR2 and Its Splicing Modulator ESRP1 Highlight the ESRP1amp-FGFR2norm-FGFR2-IIIchigh Axis in Diffuse Gastric Cancer

“…This was expected given the known role of ESRP1 in the regulation of FGFR2 alternative splicing. Our data is in accordance with previously published studies reporting the prevalence of the FGFR2-IIIb isoform in GC [40,41], although further validation at the protein level should be performed. Interestingly, we found that the increase in FGFR2-IIIb expression occurred concomitantly with a decrease in FGFR2-IIIc expression in GC.…”

“…Furthermore, in ccRCC, FGFR2-IIIc expression was found to be correlated with higher tumor grade and worse prognosis [39]. In GC, different studies have reported FGFR2-IIIb overexpression in up to 4% of analyzed cases, most of which presenting FGFR2 genetic amplification [40,41]. Of notice, Han et al showed a strong association between FGFR2-IIIb RNA and protein expression in a large GC cohort [41].…”

“…In GC, different studies have reported FGFR2-IIIb overexpression in up to 4% of analyzed cases, most of which presenting FGFR2 genetic amplification [40,41]. Of notice, Han et al showed a strong association between FGFR2-IIIb RNA and protein expression in a large GC cohort [41]. Currently, there is one clinical trial testing the efficacy of an anti-FGFR2-IIIb antibody (Bemarituzumab) in combination with FOLFOX6 in GC (clinical trial #NCT03694522).…”

FGF7/FGFR2 signal promotes invasion and migration in human gastric cancer through upregulation of thrombospondin-1

“…While increased expression of FGFR2 in gastric cancer has been reported (31,32), its role is not clear. To elucidate its role in gastric cancer, we examined FGFR2 expression in human gastric cancer tissues.…”

Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia

“…In addition to Barrett's neoplasia, FGFR2 is overexpressed in other epithelial-derived cancers, including esophageal SCC, [ 38 ] gastric, [ 39 ] esophagogastric junction, [ 40 ] colorectal, [ 41 ] pancreatic, [ 42 ] and breast [ 43 ]. We present immunofluorescence results to support broad use of this FGFR2 peptide for detection of esophageal SCC and gastric cancer, Supplementary Figures 5, 6 .…”