title: Lack of prognostic effect of carbonic anhydrase-9, hypoxia inducible factor-1α and bcl-2 in 286 patients with early squamous cell carcinoma of the glottic larynx treated with radiotherapy.
abstract: OBJECTIVE
  To evaluate the prognostic significance of potential tumour markers of hypoxia and apoptosis in early squamous cell carcinoma of the glottic larynx managed with radiotherapy.
  
  
  METHODS
  In total, 382 patients with T1 and T2 squamous cell carcinoma of the glottic larynx (vocal cords) received radical radiotherapy (50-55 Gy, in 16 fractions in 98% of cases). Pre-treatment haemoglobin was available for 328 patients; biopsy samples were available for 286. Immunohistochemistry was carried out for carbonic anhydrase-9 (CA-9), hypoxia inducible factor-1α (HIF-1α) and Bcl-2.
  
  
  RESULTS
  At 5 years, locoregional control was achieved in 88.2%, cancer-specific survival in 95.0% and overall survival in 78.7%. Adverse prognostic factors for locoregional tumour recurrence were pre-treatment haemoglobin <13.0 g/dl (P = 0.035, Log rank test; sensitivity 0.28, specificity 0.84) and stage T2 rather than T1 (P = 0.002). The effect of haemoglobin level on locoregional control was not significant when stratified by the median of 14.2 g/dl (P = 0.43) or as a continuous variable (P = 0.59). High CA-9 (P = 0.11), HIF-1α (P = 0.67) and Bcl-2 (P = 0.77) expression had no prognostic significance.
  
  
  CONCLUSIONS
  High CA-9, HIF-1α and Bcl-2 do not add to the prognostic significance of tumour stage and lower haemoglobin in predicting failure of local control in early glottic larynx squamous cell carcinoma managed with radiotherapy. The effect of haemoglobin was not strong enough to be useful as a prognostic biomarker.
authors: Department of Surgery, The Christie NHS Foundation Trust, Manchester, UK.
authors: C M
authors: CM
authors: Douglas
authors: J M
authors: JM
authors: Bernstein
authors: V E
authors: VE
authors: Ormston
authors: R C
authors: RC
authors: Hall
authors: A
authors: A
authors: Merve
authors: R
authors: R
authors: Swindell
authors: H R
authors: HR
authors: Valentine
authors: N J
authors: NJ
authors: Slevin
authors: C M L
authors: CM
authors: West
authors: J J
authors: JJ
authors: Homer
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D015687:Cell Hypoxia; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016896:Treatment Outcome; D014827:Vocal Cords / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D002256:Carbonic Anhydrases