title: Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma.
abstract: OBJECTIVE
  The purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma.
  
  
  METHODS
  THmRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance ofTHexpression in PB at diagnosis was evaluated.
  
  
  RESULTS
  THexpression was positive in 60 patients (28.6%). Fifty of 60TH-positive patients had metastatic tumors and the remaining 10 had localized tumors.THexpression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, andMYCNamplification) at diagnosis. AmongTH-positive patients, higherTHexpression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower inTH-positive patients than inTH-negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower inTH-positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). AmongTH-positive patients, a higher expression level ofTHwas associated with a worse outcome. In multivariate analyses, positiveTHexpression in PB at diagnosis was an independent poor prognostic factor for PFS.
  
  
  CONCLUSIONS
  The treatment intensity should be tailored according toTHexpression in PB at diagnosis.
authors.affiliation: Department of Pediatrics, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
authors.forename: Na Hee
authors.initials: NH
authors.lastname: Lee
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Meong Hi
authors.initials: MH
authors.lastname: Son
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eunsang
authors.initials: E
authors.lastname: Yi
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood*; D012307:Risk Factors; D014446:Tyrosine 3-Monooxygenase / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D014446:Tyrosine 3-Monooxygenase
keywords: Neuroblastoma; Polymerase chain reaction; Tyrosine 3-monooxygenase