title: P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy.
abstract: OBJECTIVE
  P53 and Ki-67 status will predict response to treatment, organ preservation, and survival in patients with advanced squamous cell cancers of the head and neck treated with chemoradiotherapy (CRT).
  
  
  METHODS
  Retrospective analysis of p53 and Ki-67 status from the CRT arm of a randomized, controlled trial (n = 50) and from patients receiving the same treatment but not enrolled in the trial (n = 55).
  
  
  METHODS
  P53 and Ki-67 status were established from archived tissue samples using immunohistochemical (IHC) staining. Tumors were positive for p53 (p53+) when more than 2% of cells stained for p53 and were positive for Ki-67 (Ki-67+) when any cell stained for Ki-67. End points were tumor response, tumor recurrence, survival status, and organ preservation at last follow-up, and time to events. Predictive models were calculated for each outcome.
  
  
  RESULTS
  Neither marker predicted tumor response to treatment. P53+ status was associated with tumor recurrence (P =.003) and locoregional recurrence (P =.003). Adjusting for time to event, p53+ status was significantly related to a lower recurrence-free survival (P =.004), lower disease-specific survival (P =.04), lower overall survival with primary site preservation (P =.03), and lower disease-specific survival with primary site preservation (P =.003). Multivariate analysis revealed that p53+ status was significantly related to a lower recurrence-free survival (P =.01, risk ratio [RR] = 3.65) and lower disease-specific survival with organ preservation (P =.02, RR = 3.41). Ki-67+ status was not related to any variables. However, multivariate analysis revealed that Ki-67+ was significantly related to a lower overall survival (P =.05, RR = 2.03). The combination of both markers negative (p53-/Ki-67-) was associated with a lower incidence of tumor recurrence (P =.02), lower locoregional recurrence (P =.01), and fewer second primary lesions (P =.04). Adjusting for time to event, p53-/Ki-67- status was significantly related to a higher recurrence-free survival (P =.02), higher disease-specific survival with primary site preservation (P =.02), and higher overall survival with primary site preservation (P =.02). Multivariate analysis revealed that p53-/Ki-67- status was significantly related to a higher overall survival with site preservation (P =.01, RR = 2.78).
  
  
  CONCLUSIONS
  P53 and Ki-67 status appear to be related to the various survival end points considered in this study. However, this relation does not seem to be sufficient to warrant treatment modifications. Closer follow-up may be justified in both p53+ and Ki67+ patients to detect recurrence or a second primary at an earlier stage, possibly improving survival.
authors.affiliation: Department of Otolaryngology and Head & Neck Surgery, University Hospital of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: P
authors.initials: P
authors.lastname: Lavertu
authors.forename: D J
authors.initials: DJ
authors.lastname: Adelstein
authors.forename: J
authors.initials: J
authors.lastname: Myles
authors.forename: M
authors.initials: M
authors.lastname: Secic
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53