High amplification of FGFR1 gene is a delayed poor prognostic factor in early stage ESCC patients
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Qi Song1,*, Yalan Liu1,*, Dongxian Jiang1, Haixing Wang1, Jie Huang1, Yifan Xu1, Akesu Sujie1, Haiying Zeng1, Chen Xu1 and Yingyong Hou1,2
1Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China
2Department of Pathology, School of Basic Medical Sciences & Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China
*These authors have contributed equally to this work
Yingyong Hou, email: [email protected]
Chen Xu, email: [email protected]
Keywords: FGFR1 high amplification, clinical stage, disease free survival time, prognostic marker, ESCC
Received: October 17, 2016 Accepted: June 29, 2017 Published: August 12, 2017
Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to FGFR inhibitors. The aim of this study was to investigate the frequency and the prognostic impact of FGFR1 amplification in patients with resected esophageal squamous cell carcinoma (ESCC) by using fluorescent in situ hybridization. Microarrayed paraffin embedded blocks were constructed, and the cohort of tissues came from 506 patients with ESCC. FGFR1 high amplification (FGFR1high) was defined by an FGFR1/centromere 8 ratio of ≥ 2.0, or average number of FGFR1 signals/tumor cell nucleus ≥ 6.0, or percentage of tumor cells containing ≥ 15 FGFR1 signals, or large cluster in ≥ 10% of cancer cells. FGFR1 low amplification was defined by ≥ 5 FGFR1 signals in ≥ 50% of cancer cells. Kaplan-Meier curves with log-rank tests and Cox proportional hazards model were used to analyze patients’ survival. Among 506 patients, high amplification, low amplification, and disomy were detected in 8.7%, 3.6% and 87.7%, respectively. In general, the FGFR1high group trended towards worse disease-free survival (DFS) and overall survival (OS) compared to the FGFR1 low amplification/disomy (FGFR1low/disomy) group (DFS, P=0.108; OS, P=0.112), but this trend was amplified for patients with DFS ≥ 30 months (DFS, P=0.009; OS, P=0.007). Furthermore, when patients were stratified into stage I-II and stage III-IV, the FGFR1high group directly presented with adverse DFS and OS than the FGFR1low/disomy group in stage I-II patients (DFS, P=0.019; OS, P=0.034), especially with DFS ≥ 30 months (DFS, P=0.002; OS, P=0.001). However, for patients in stage III-IV, FGFR1high had no effect on prognosis regardless of DFS time. FGFR1high occurs in a minority of ESCC, and it predicts delayed poor prognosis in stage I and II ESCC patients.
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