title: Fibroblast growth factor receptor 2 gene amplification status and its clinicopathologic significance in gastric carcinoma.
abstract: Fibroblast growth factor receptor 2 is a member of receptor tyrosine kinase family, and fibroblast growth factor receptor 2 gene amplification or missense mutation has been observed in various human cancers, including gastric carcinoma. Recent studies have shown that anti-fibroblast growth factor receptor 2 agents inhibit tumor progression in various human cancers, such as endometrial carcinoma and gastric carcinoma, which remains one of the most frequent causes of cancer-related death worldwide. We considered that knowledge of the status of fibroblast growth factor receptor 2 gene amplification in gastric carcinoma might aid in targeted cancer therapy. In this study, fibroblast growth factor receptor 2 amplification status was evaluated by fluorescence in situ hybridization in 313 surgically resected gastric carcinoma tissues, and the results were validated by quantitative real-time polymerase chain reaction. In addition, potential associations between clinicopathologic parameters and the presence of fibroblast growth factor receptor 2 amplification were investigated, and survival analysis was performed. Of the 313 cases, 14 (4.5%) showed fibroblast growth factor receptor 2 amplification by fluorescence in situ hybridization. Fibroblast growth factor receptor 2 amplification was found to be associated with a higher pT stage (P = .023), higher pN stage (P = .038), and distant metastasis (P = .009) and to be significantly associated with lower cancer-specific survival by univariate analysis (P = .012). Gastric carcinoma with fibroblast growth factor receptor 2 amplification was found to be associated with advanced disease and a poor prognosis. We believe that the determination of fibroblast growth factor receptor 2 amplification status could allow the identification of a subset of cancers sensitive to targeted fibroblast growth factor receptor 2 inhibitor-based therapy.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jung
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Jung
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Min
authors.forename: Min A
authors.initials: MA
authors.lastname: Kim
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D051497:Receptor, Fibroblast Growth Factor, Type 2