FGFR2 gene amplification status and its clinicopathologic significance in gastric carcinoma

다국어 초록 (Multilingual Abstract)

Introduction : Fibroblast growth factor receptor 2 (FGFR2) is a member of the FGFR receptor tyrosine kinase family, and FGFR2 gene amplification or missense mutation has been observed in various human cancers, including gastric carcinoma. Furthermore, recent studies have shown that anti-FGFR2 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 FGFR2 gene amplification in gastric carcinoma may aid in targeted cancer therapy. Methods: In this study, FGFR2 amplification status was evaluated using fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (PCR) in 313 surgically resected gastric carcinoma tissues. FGFR2 gene copy number alteration was also evaluated in 372 gastric carcinoma tissues by FISH method. In addition, potential associations between clinicopathological parameters and the presence of FGFR2 amplification or copy number gain was investigated and survival analysis was performed Results: In our study, the frequency of FGFR2 amplification was 4.0% and 4.5% in the 2 groups of patients. FGFR2 amplification was also found to be associated with a higher pathologic T stage (p=0.023), pathologic N stage (p=0.038) and distant metastasis (p=0.009). In addition, univariate analysis revealed that FGFR2 copy number gain as well as amplification was significantly associated with lower cancer-specific survival. Conclusion: We therefore found gastric carcinoma with FGFR2 amplification or FGFR2 copy number gain to be associated with advanced disease. We believe that the determination of FGFR2 gene status could allow the identification of a subset of cancers sensitive to targeted FGFR2 inhibitor - based therapies.

목차 (Table of Contents)

• Introduction 1
• Materials and Methods 5
• Results 14
• Discussion 45
• References 52
• Abstract (Korean) 60