title: Loss of MTBP expression is associated with reduced survival in a biomarker-defined subset of patients with squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta-analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous.
  
  
  METHODS
  The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses.
  
  
  RESULTS
  Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2-low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log-rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12-2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log-rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39-5.54) in p53 + ve/MDM2-low patients.
  
  
  CONCLUSIONS
  These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status-dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression.
authors.affiliation: School of Cancer Studies, The University of Liverpool, Liverpool, UK. vlatko@liv.ac.uk
authors.forename: Nikolina
authors.initials: N
authors.lastname: Vlatković
authors.forename: Ashraf
authors.initials: A
authors.lastname: El-Fert
authors.forename: Timothy
authors.initials: T
authors.lastname: Devling
authors.forename: Arpita
authors.initials: A
authors.lastname: Ray-Sinha
authors.forename: David M
authors.initials: DM
authors.lastname: Gore
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Rubbi
authors.forename: Andy
authors.initials: A
authors.lastname: Dodson
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Jones
authors.forename: Tim R
authors.initials: TR
authors.lastname: Helliwell
authors.forename: Terence M
authors.initials: TM
authors.lastname: Jones
authors.forename: Mark T
authors.initials: MT
authors.lastname: Boyd
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D018307:Neoplasms, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C485931:MTBP protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2