Fibroblast growth factor receptor 1 gene amplification is associated with poor survival in patients with resected esophageal squamous cell carcinoma.

Abstract

To investigate the frequency and the prognostic impact of fibroblast growth factor receptor 1 (FGFR1) gene amplification in 526 curatively resected esophageal squamous cell carcinoma (ESCC). Using fluorescent in situ hybridization, high amplification was defined by an FGFR1/centromer 8 ratio is ≥ 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%. Low amplification was defined by ≥ 5 FGFR1 signals in ≥ 50%. FGFR2 and FGFR3 mutations were assessed by direct sequencing in 388 cases and no mutation was detected. High and low amplification were detected in 8.6% and 1.1%, respectively. High FGFR1 amplification had significantly shorter disease-free survival (34.0 vs 158.5 months P=0.019) and overall survival (52.2 vs not reached P=0.022) than low/no amplification group. After adjusting for sex, smoking, stage, histology, and adjuvant treatment, high FGFR1 amplification had a greater risk of recurrence (adjusted hazard ratio [AHR], 1.6; P=0.029) and death (AHR, 1.53; P=0.050). High amplification was significantly higher in current smokers than former and never-smokers (Ptrend<0.001) and increased proportional to smoking dosage. High FGFR1 amplification is a frequent oncogenic alteration and an independent poor prognostic factor in resected ESCC.

• Authors: Hyo Song Kim, Seung Eun Lee, Yoon Sung Bae, Dae Joon Kim, Chang-Geol Lee, Jin Hur, Hyunsoo Chung, Jun Chul Park, Da Hyun Jung, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Hye Ryun Kim, Yong Wha Moon, Joo Hang Kim, Young Mog Shim, Susan S Jewell, Hyunki Kim, Yoon-La Choi, Byoung Chul Cho
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 4 Pg. 2562-72 (Feb 10 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25537505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FGFR1 protein, human
• Receptor, Fibroblast Growth Factor, Type 1

Topics

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Squamous Cell (genetics, pathology, therapy)
• Disease-Free Survival
• Esophageal Neoplasms (genetics, pathology, therapy)
• Female
• Gene Amplification
• Humans
• In Situ Hybridization, Fluorescence
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Prognosis
• Receptor, Fibroblast Growth Factor, Type 1 (genetics)
• Risk Factors
• Smoking