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, Byoung Chul Cho

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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 (P trend < 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.

Original languageEnglish
Pages (from-to)2562-2572
Number of pages11
JournalOncotarget
Volume6
Issue number4
DOIs
Publication statusPublished - 2015 Jan 1

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Receptor, Fibroblast Growth Factor, Type 1
Gene Amplification
Survival
Smoking
Mutation
Esophageal Squamous Cell Carcinoma
Cell Nucleus
Fluorescence In Situ Hybridization
Disease-Free Survival
Neoplasms
Histology
Recurrence

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Kim, Hyo Song ; Lee, Seung Eun ; Bae, Yoon Sung ; Kim, Dae Joon ; Lee, Chang Geol ; Hur, Jin ; Chung, Hyunsoo ; Park, Jun Chul ; Jung, Da Hyun ; Shin, Sung Kwan ; Lee, Sang Kil ; Lee, Yong Chan ; Kim, Hye Ryun ; Moon, Yong Wha ; Kim, Joo Hang ; Shim, Young Mog ; Jewell, Susan S. ; Kim, Hyunki ; Choi, Yoon La ; Cho, Byoung Chul. / Fibroblast growth factor receptor 1 gene amplification is associated with poor survival in patients with resected esophageal squamous cell carcinoma. In: Oncotarget. 2015 ; Vol. 6, No. 4. pp. 2562-2572.
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title = "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 (P trend < 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.",
author = "Kim, {Hyo Song} and Lee, {Seung Eun} and Bae, {Yoon Sung} and Kim, {Dae Joon} and Lee, {Chang Geol} and Jin Hur and Hyunsoo Chung and Park, {Jun Chul} and Jung, {Da Hyun} and Shin, {Sung Kwan} and Lee, {Sang Kil} and Lee, {Yong Chan} and Kim, {Hye Ryun} and Moon, {Yong Wha} and Kim, {Joo Hang} and Shim, {Young Mog} and Jewell, {Susan S.} and Hyunki Kim and Choi, {Yoon La} and Cho, {Byoung Chul}",
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Kim, HS, Lee, SE, Bae, YS, Kim, DJ, Lee, CG, Hur, J, Chung, H, Park, JC, Jung, DH, Shin, SK, Lee, SK, Lee, YC, Kim, HR, Moon, YW, Kim, JH, Shim, YM, Jewell, SS, Kim, H, Choi, YL & Cho, BC 2015, 'Fibroblast growth factor receptor 1 gene amplification is associated with poor survival in patients with resected esophageal squamous cell carcinoma', Oncotarget, vol. 6, no. 4, pp. 2562-2572. https://doi.org/10.18632/oncotarget.2944

Fibroblast growth factor receptor 1 gene amplification is associated with poor survival in patients with resected esophageal squamous cell carcinoma. / Kim, Hyo Song; Lee, Seung Eun; Bae, Yoon Sung; Kim, Dae Joon; Lee, Chang Geol; Hur, Jin; Chung, Hyunsoo; Park, Jun Chul; Jung, Da Hyun; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan; Kim, Hye Ryun; Moon, Yong Wha; Kim, Joo Hang; Shim, Young Mog; Jewell, Susan S.; Kim, Hyunki; Choi, Yoon La; Cho, Byoung Chul.

In: Oncotarget, Vol. 6, No. 4, 01.01.2015, p. 2562-2572.

Research output: Contribution to journalArticle

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T1 - Fibroblast growth factor receptor 1 gene amplification is associated with poor survival in patients with resected esophageal squamous cell carcinoma

AU - Kim, Hyo Song

AU - Lee, Seung Eun

AU - Bae, Yoon Sung

AU - Kim, Dae Joon

AU - Lee, Chang Geol

AU - Hur, Jin

AU - Chung, Hyunsoo

AU - Park, Jun Chul

AU - Jung, Da Hyun

AU - Shin, Sung Kwan

AU - Lee, Sang Kil

AU - Lee, Yong Chan

AU - Kim, Hye Ryun

AU - Moon, Yong Wha

AU - Kim, Joo Hang

AU - Shim, Young Mog

AU - Jewell, Susan S.

AU - Kim, Hyunki

AU - Choi, Yoon La

AU - Cho, Byoung Chul

PY - 2015/1/1

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N2 - 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 (P trend < 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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