title: Biomarkers in advanced larynx cancer.
abstract: OBJECTIVE
  To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial.
  
  
  METHODS
  Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers, and correlations with outcome were determined.
  
  
  METHODS
  Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers.
  
  
  RESULTS
  Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (P = 0.0003).
  
  
  CONCLUSIONS
  Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Medical School, Ohio State University, Columbus, Ohio.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
authors.forename: Emily
authors.initials: E
authors.lastname: Bellile
authors.forename: Julia
authors.initials: J
authors.lastname: Lee
authors.forename: Jeremy
authors.initials: J
authors.lastname: Taylor
authors.forename: Nisha
authors.initials: N
authors.lastname: D'Silva
authors.forename: Kitrina
authors.initials: K
authors.lastname: Cordell
authors.forename: Celina
authors.initials: C
authors.lastname: Kleer
authors.forename: Robbi
authors.initials: R
authors.lastname: Kupfer
authors.forename: Pawan
authors.initials: P
authors.lastname: Kumar
authors.forename: Susan
authors.initials: S
authors.lastname: Urba
authors.forename: Francis
authors.initials: F
authors.lastname: Worden
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.forename: Mark E P
authors.initials: ME
authors.lastname: Prince
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Chepeha
authors.forename: Norman D
authors.initials: ND
authors.lastname: Hogikyan
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Moyer
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: EGFR; Laryngeal cancer or carcinoma; biomarkers; cyclin D1; p53