title: Prognostic implications ofFGFR1andMYCstatus in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  To investigate the clinicopathological features and prognostic implications of combined MYC and fibroblast growth factor receptor 1 (FGFR1) status in esophageal squamous cell carcinomas (ESCCs).
  
  
  METHODS
  All patients with ESCC (n= 180) underwent surgical resection at Seoul National University Hospital sometime between 2000 and 2013. A tissue microarray was constructed using cores obtained from representative tumor areas of formalin-fixed, paraffin-embedded tissue blocks.FGFR1andMYCcopy numbers were quantified using fluorescencein situhybridization. The level of MYC expression was determined using immunohistochemistry.FGFR1andMYCamplification status was compared between primary and metastatic lymph nodes. Univariate and multivariate survival analyses were performed according to adjuvant therapy status.
  
  
  RESULTS
  FGFR1andMYCamplifications were observed in 21.4% (37/173) and 54.2% (91/168) of patients, respectively, while MYC expression was observed in 58.9% (106/180) of patients. There was a positive correlation betweenMYCamplification and overexpression (P= 0.002). AlthoughFGFR1amplification was not associated withMYCamplification or expression, 12.3% (20/163) of patients exhibited bothFGFR1amplification and MYC expression. There was also a correlation inFGFR1amplification status between matched primary tumors and metastatic lymph nodes (P< 0.001). MYC expression was higher in ESCCs with pT1 (P< 0.001) and in those with no lymph node metastasis (P= 0.023). MYC expression was associated with prolonged disease-free survival (P= 0.036) and overall survival (OS) (P= 0.017) but was not an independent prognostic factor.FGFR1amplification was an independent predictor for prolonged OS in all patients (P= 0.029) and in those who did not receive adjuvant therapy (P= 0.013). CombinedFGFR1amplification and MYC expression predicted better OS in patients who did not receive adjuvant therapy (P= 0.034) but not in those who did receive adjuvant therapy.
  
  
  CONCLUSIONS
  FGFR1amplification and MYC expression have prognostic implications in resected ESCCs with respect to adjuvant therapy. The role of FGFR1-targeted therapy in ESCC remains to be explored.
authors.affiliation: Dohee Kwon, Ji Yun Yun, Yoon Kyung Jeon, Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea.
authors.forename: Dohee
authors.initials: D
authors.lastname: Kwon
authors.affiliation: Dohee Kwon, Ji Yun Yun, Yoon Kyung Jeon, Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Yun
authors.affiliation: Dohee Kwon, Ji Yun Yun, Yoon Kyung Jeon, Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Dohee Kwon, Ji Yun Yun, Yoon Kyung Jeon, Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Dohee Kwon, Ji Yun Yun, Yoon Kyung Jeon, Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D010641:Phenotype; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D018714:Radiotherapy, Adjuvant; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Esophageal squamous cell carcinoma; Fibroblast growth factor receptor 1; Fluorescent in situ hybridization; Gene amplification; MYC; Prognosis; Receptor tyrosine kinase