title: Prognostic value of hypoxia-associated markers in advanced larynx and hypopharynx squamous cell carcinoma.
abstract: OBJECTIVE
  To determine the prognostic value of hypoxia-associated markers carbonic anhydrase-9 (CA-9) and hypoxia-inducible factor-1α (HIF-1α) in advanced larynx and hypopharynx squamous cell carcinoma (SCCa) treated by organ preservation strategies.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Pretreatment CA-9 and HIF-1α expression, clinicopathologic data, and tumor volume were analyzed in a series of 114 patients with T3-4 SCCa larynx or hypopharynx treated by (chemo)radiation.
  
  
  RESULTS
  Adverse prognostic factors for locoregional control were T4 classification (P = 0.008), and for disease-specific survival were CA-9 positivity (P = 0.039), T4 classification (P = 0.001), larger tumor volume (P = 0.004), N1-3 classification (P = 0.002), and pretreatment hemoglobin < 13.0 g/dl (P = 0.014). With increasing CA-9 expression, there was a trend to increasing tumor recurrence (P trend = 0.009) and decreasing survival (P trend = 0.002). On multivariate analysis, independent variables were T4 classification (hazard ratio [HR] 13.54, P = 0.01) for locoregional failure, and CA-9 positivity (HR = 8.02, P = 0.042) and higher tumor volume (HR = 3.33, P = 0.007) for disease-specific mortality.
  
  
  CONCLUSIONS
  This is the first study to look specifically at T3 and T4 SCCa larynx and hypopharynx for a relationship between hypoxia-associated marker expression and clinical outcome. Pretreatment immunohistochemical CA-9 expression is an adverse prognostic factor for disease-specific survival, indicating that CA-9 expression may confer a more aggressive tumor phenotype.
authors.affiliation: University Department of Otolaryngology-Head & Neck Surgery, Manchester Royal Infirmary and Manchester Academic Health Science Centre; Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Bernstein
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Andrews
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Slevin
authors.forename: Catharine M L
authors.initials: CM
authors.lastname: West
authors.forename: Jarrod J
authors.initials: JJ
authors.lastname: Homer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology*; D007013:Hypopharynx / Q000473:pathology; D000860:Hypoxia / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood; D007124:Immunoenzyme Techniques; D007822:Laryngeal Neoplasms / Q000401:mortality / Q000473:pathology*; D007830:Larynx / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D047368:Tumor Burden / Q000502:physiology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: CA-9; HIF-1α; Head and neck squamous cell carcinoma; biomarker; hypopharynx; larynx; tumor hypoxia; tumor volume