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

Kim HS, Lee SE, Bae YS, Kim DJ, Lee CG, Hur J, Chung H, Park JC, Jung da H, Shin SK, Lee SK, Lee YC, Kim HR, Moon YW, Kim JH, Shim YM, Jewell SS, Kim H, Choi YL, Cho BC - Oncotarget (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

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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Fibroblast growth factor receptor 1 (FGFR1) amplification assessed by fluorescent in situ hybridization(A) High FGFR1 amplification; (B) Low FGFR1 amplification; (C) No amplification.
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Figure 1: Fibroblast growth factor receptor 1 (FGFR1) amplification assessed by fluorescent in situ hybridization(A) High FGFR1 amplification; (B) Low FGFR1 amplification; (C) No amplification.

Mentions: Among 526 patients, 45 (8.6%) were high FGFR1 amplification, 6 (1.1%) were low FGFR1 amplification, and 475 (90.3%) displayed no amplification (Table 1; Figure 1). The median FGFR1 gene copy number per nucleus and the mean FGFR1/CEN8 ratio in all patients were 2.2 (range, 0 to 15.5 copies per nucleus) and 1.5 (range, 0 to 7.8). The median FGFR1 gene copy number was 6.4 (range, 4.1 to 15.5) in high amplification, 5.1 (range, 5.0 to 5.6) in low amplification, and 2.2 (range 0 to 5.7) in no amplification group. The mean FGFR1/CEN8 ratio was 2.9 (range 1.1 to 7.8), 1.5 (range, 1.0 to 1.9), and 1.3 (range, 0 to 1.6) in high, low and no amplification group, respectively. Of 45 high FGFR1 amplified tumors, 12 cases (26.7%) only satisfied the criterion of an FGFR1:CEN8 ratio of ≥ 2.0, 7 cases (15.6%) only satisfied the criterion of an average number of FGFR1 signal per nucleus ≥6.0, and 4 cases (8.9%) only satisfied the criterion of percentage of tumor cells containing ≥ 15 FGFR1 signals or large clusters in ≥ 10% cells, respectively. 22 cases (48.9%) satisfied all three criteria for FGFR1 amplification simultaneously.


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

Kim HS, Lee SE, Bae YS, Kim DJ, Lee CG, Hur J, Chung H, Park JC, Jung da H, Shin SK, Lee SK, Lee YC, Kim HR, Moon YW, Kim JH, Shim YM, Jewell SS, Kim H, Choi YL, Cho BC - Oncotarget (2015)

Fibroblast growth factor receptor 1 (FGFR1) amplification assessed by fluorescent in situ hybridization(A) High FGFR1 amplification; (B) Low FGFR1 amplification; (C) No amplification.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385871&req=5

Figure 1: Fibroblast growth factor receptor 1 (FGFR1) amplification assessed by fluorescent in situ hybridization(A) High FGFR1 amplification; (B) Low FGFR1 amplification; (C) No amplification.
Mentions: Among 526 patients, 45 (8.6%) were high FGFR1 amplification, 6 (1.1%) were low FGFR1 amplification, and 475 (90.3%) displayed no amplification (Table 1; Figure 1). The median FGFR1 gene copy number per nucleus and the mean FGFR1/CEN8 ratio in all patients were 2.2 (range, 0 to 15.5 copies per nucleus) and 1.5 (range, 0 to 7.8). The median FGFR1 gene copy number was 6.4 (range, 4.1 to 15.5) in high amplification, 5.1 (range, 5.0 to 5.6) in low amplification, and 2.2 (range 0 to 5.7) in no amplification group. The mean FGFR1/CEN8 ratio was 2.9 (range 1.1 to 7.8), 1.5 (range, 1.0 to 1.9), and 1.3 (range, 0 to 1.6) in high, low and no amplification group, respectively. Of 45 high FGFR1 amplified tumors, 12 cases (26.7%) only satisfied the criterion of an FGFR1:CEN8 ratio of ≥ 2.0, 7 cases (15.6%) only satisfied the criterion of an average number of FGFR1 signal per nucleus ≥6.0, and 4 cases (8.9%) only satisfied the criterion of percentage of tumor cells containing ≥ 15 FGFR1 signals or large clusters in ≥ 10% cells, respectively. 22 cases (48.9%) satisfied all three criteria for FGFR1 amplification simultaneously.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

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.

Show MeSH
Related in: MedlinePlus