P-005 Clinical significance of Eph, FGFR, and PDGF expressions in advanced gastric cancers

Abstract

Introduction: Various tyrosine kinases receptors and those ligands are involved in growth of malignant disease. Many studies showed the relation between HER1, HER2, VEGFRs, or cMET and gastric cancers. Inhibition of HER2 or VEGFR has been used for treatment for unresectable or metastatic gastric cancer in clinical practice. In this study, we investigated expression of EphA1, EphA2, EphA4, ephrinA1, FGFR1, FGFR 2, FGFR 4, PDGFC, and PDGFD and evaluated the relation to clinical outcomes in advanced gastric cancers resected completely, because those expressions was involved with tumor progression of gastric cancer in our previous studies.Methods: Our study group comprised 117 patients with primary advanced gastric adenocarcinoma who underwent surgical complete resection between 2003 and 2007 in the Department of Esophagogastric Surgery, Tokyo Medical and Dental University. The expression of EphA1, A2, A4, ephrinA1, FGFR1, 2, 4, PDGFC, and PDGFD was measured in the resected tumors by immunohistochemical analysis. Interpretation of immunostaining results was based on a scoring system comprised of both staining intensity and extensity.Results: Based on the 7th TNM classification, T2, T3, and T4 tumors were 26, 32, and 43%, and N0, N1, N2, and N3 tumors were 34, 17, 21, and 27%. Stage IB, II, and III tumors were17, 30, and 53%. Overexpression of EphA1, EphA2, EphA4, ephrinA1, FGFR1, FGFR 2, FGFR 4, PDGFC, and PDGFD were 74, 79, 67, 61, 41, 64, 91, 61, and 85%. Serosa invasion was significantly associated with high expression of EphA2, EphA4, and PDGFD (p = 0.01, 0.025, and 0.015) and lymph node metastasis was done with EphA2, EphA4, and FGFR4 (p = 0.01, 0.006, and 0.044). Stage III significantly related to EphA4, FGFR4, and PDGFC (p = 0.005, 0.021, and 0.01). On univariate analysis of relapse-free survival, overexpression of EphA2, EphA4, or PDGFD was significantly associated with poor survival (p = 0.015, 0.001, and 0.046). EphA4 was an independent prognostic factor (HR = 2.4, 95% CI: 1.1-5.4; p = 0.034)Conclusion: Eph, FGFR, or PDGF overexpressed in many patients with advanced gastric cancer. The expression of EphA2, EphA4, or PDGFD was significantly associated with survival of those patients. EphA4 might become a prognostic factor in those patients. Introduction: Various tyrosine kinases receptors and those ligands are involved in growth of malignant disease. Many studies showed the relation between HER1, HER2, VEGFRs, or cMET and gastric cancers. Inhibition of HER2 or VEGFR has been used for treatment for unresectable or metastatic gastric cancer in clinical practice. In this study, we investigated expression of EphA1, EphA2, EphA4, ephrinA1, FGFR1, FGFR 2, FGFR 4, PDGFC, and PDGFD and evaluated the relation to clinical outcomes in advanced gastric cancers resected completely, because those expressions was involved with tumor progression of gastric cancer in our previous studies. Methods: Our study group comprised 117 patients with primary advanced gastric adenocarcinoma who underwent surgical complete resection between 2003 and 2007 in the Department of Esophagogastric Surgery, Tokyo Medical and Dental University. The expression of EphA1, A2, A4, ephrinA1, FGFR1, 2, 4, PDGFC, and PDGFD was measured in the resected tumors by immunohistochemical analysis. Interpretation of immunostaining results was based on a scoring system comprised of both staining intensity and extensity. Results: Based on the 7th TNM classification, T2, T3, and T4 tumors were 26, 32, and 43%, and N0, N1, N2, and N3 tumors were 34, 17, 21, and 27%. Stage IB, II, and III tumors were17, 30, and 53%. Overexpression of EphA1, EphA2, EphA4, ephrinA1, FGFR1, FGFR 2, FGFR 4, PDGFC, and PDGFD were 74, 79, 67, 61, 41, 64, 91, 61, and 85%. Serosa invasion was significantly associated with high expression of EphA2, EphA4, and PDGFD (p = 0.01, 0.025, and 0.015) and lymph node metastasis was done with EphA2, EphA4, and FGFR4 (p = 0.01, 0.006, and 0.044). Stage III significantly related to EphA4, FGFR4, and PDGFC (p = 0.005, 0.021, and 0.01). On univariate analysis of relapse-free survival, overexpression of EphA2, EphA4, or PDGFD was significantly associated with poor survival (p = 0.015, 0.001, and 0.046). EphA4 was an independent prognostic factor (HR = 2.4, 95% CI: 1.1-5.4; p = 0.034) Conclusion: Eph, FGFR, or PDGF overexpressed in many patients with advanced gastric cancer. The expression of EphA2, EphA4, or PDGFD was significantly associated with survival of those patients. EphA4 might become a prognostic factor in those patients.