title: Fibroblast growth factor receptor 4 protein expression and clinicopathological features in gastric cancer.
abstract: OBJECTIVE
  To investigate fibroblast growth factor receptor 4 (FGFR4) protein expression in Chinese patients with resectable gastric cancer (GC) and the association with clinicopathological characteristics and survival.
  
  
  METHODS
  One hundred and seventy-five GC patients who underwent curative surgical procedures were enrolled in this study. The protein expression of FGFR4 in formalin-fixed, paraffin-embedded (FFPE) GC tissues was determined by immunohistochemical (IHC) analysis. Patient clinicopathological data and survival information were also collected and χ(2) statistical analysis was performed to analyze FGFR4 protein expression in the subgroups with differing clinicopathological characteristics including; gender, age, tumor location, differentiation, tumor-node-metastasis stage, macroscopic type, depth of invasion, lymph node metastases, distant metastasis, neural invasion and vascular invasion. Furthermore, some common molecular markers of GC in our cancer center, including p53, p27, topoisomerase IIα (Topo IIα) were also determined by IHC and their association with FGFR4 protein expression evaluated. The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using the log rank test.
  
  
  RESULTS
  Seventy seven cases (44%) were found to have high expression of FGFR4 protein. Significantly different FGFR4 expression was observed between gastric cancers with differing expression of Topo IIα (log rank χ(2) = 9.4760, P = 0.0236). No significant differences were observed between subgroups defined by any of the other clinicopathological characteristics. The median survival time of the FGFR4 high expression (77 cases) and low expression groups (98 cases) was 27 mo and 39 mo, respectively. The five-year survival rates and median survival times of gastric cancers with high FGFR4 expression were worse than those with low expression (30.8% vs 39.2%, 27 mo vs 39 mo), respectively, however, no significant difference was observed in survival time (log rank χ(2) = 1.0477, P = 0.3060). Survival analysis revealed that high expression of FGFR4 was a predictor of poor outcome in GC patients if the tumor was small (less than or equal to 3 cm in size) (log rank χ(2) = 5.5033, P = 0.0190), well differentiated (log rank χ(2) = 7.9757, P = 0.0047), and of T1 or T2 stage invasion depth (log rank χ(2) = 4.8827, P = 0.0271).
  
  
  CONCLUSIONS
  Our results suggest that high tumor expression of FGFR4 protein is not an independent risk factor for GC cancer initiation, but is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or in the early stages of invasion.
authors: Hao Chen, Dan-Ping Shen, Zi-Zhen Zhang, Jia-Hua Liu, Xing-Zhi Ni, Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors: Hao
authors: H
authors: Chen
authors: Hao Chen, Dan-Ping Shen, Zi-Zhen Zhang, Jia-Hua Liu, Xing-Zhi Ni, Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors: Dan-Ping
authors: DP
authors: Shen
authors: Hao Chen, Dan-Ping Shen, Zi-Zhen Zhang, Jia-Hua Liu, Xing-Zhi Ni, Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors: Zi-Zhen
authors: ZZ
authors: Zhang
authors: Hao Chen, Dan-Ping Shen, Zi-Zhen Zhang, Jia-Hua Liu, Xing-Zhi Ni, Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors: Jia-Hua
authors: JH
authors: Liu
authors: Hao Chen, Dan-Ping Shen, Zi-Zhen Zhang, Jia-Hua Liu, Xing-Zhi Ni, Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors: Yan-Ying
authors: YY
authors: Shen
authors: Hao Chen, Dan-Ping Shen, Zi-Zhen Zhang, Jia-Hua Liu, Xing-Zhi Ni, Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors: Xing-Zhi
authors: XZ
authors: Ni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4
keywords: Clinicopathological characteristics; Fibroblast growth factor receptor 4; Gastric cancer; Prognosis; Protein expression