Oncotarget

Clinical Research Papers:

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

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 and Byoung Chul Cho _

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Oncotarget. 2015; 6:2562-2572. https://doi.org/10.18632/oncotarget.2944

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Abstract

Hyo Song Kim1,*, Seung Eun Lee2,*, Yoon Sung Bae3,*, Dae Joon Kim4, Chang-Geol Lee5, Jin Hur6, Hyunsoo Chung7, Jun Chul Park7, Da Hyun Jung7, Sung Kwan Shin7, Sang Kil Lee7, Yong Chan Lee7, Hye Ryun Kim1, Yong Wha Moon1, Joo Hang Kim1, Young Mog Shim8, Susan S. Jewell9, Hyunki Kim3, Yoon-La Choi2 and Byoung Chul Cho1

1 Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

2 Departments of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

3 Department of Pathology, Yonsei University College of Medicine, Seoul, Korea

4 Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea

5 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea

6 Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea

7 Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

8 Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

9 Abbott Molecular Laboratories, Des Plaines, IL

* These authors contributed equally to this work as co-first authors

Correspondence:

Byoung Chul Cho, email:

Yoon-La Choi, email:

Hyunki Kim, email:

Keywords: Fibroblast growth factor receptor 1, esophageal squamous cell carcinoma, gene amplification, fluorescent in situ hybridization, prognostic factor

Received: September 11, 2014 Accepted: December 09, 2014 Published: December 10, 2014

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.


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