title: Association of keratinization with 5-year disease-specific survival in oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  Keratinization is a histologic feature on hematoxylin-eosin staining associated with adverse outcomes in head and neck cancer, particularly oral cavity squamous cell carcinoma. However, the prognostic value of keratinization has not been demonstrated in oropharyngeal squamous cell carcinoma (OPSCC) in a large cohort of patients.
  
  
  OBJECTIVE
  To quantify the prognostic value of keratinization in a large cohort of patients with OPSCC with subgroup analysis based on p16 status, basaloid differentiation, and smoking status.
  
  
  METHODS
  Retrospective cross-sectional study using a prospectively collected database that identified 208 patients with OPSCC diagnosed and treated at a single tertiary cancer center from 2002 to 2009. Tissue microarrays (TMAs) were generated from 208 patient specimens stained with hematoxylin-eosin and immunohistochemical markers. Digital images from stained TMAs were scored for the presence of keratinization and/or basaloid differentiation and for p16 status.
  
  
  METHODS
  Patients were treated with curative intent with surgery, radiation, and/or chemotherapy.
  
  
  METHODS
  The primary outcome measure was 5-year disease-specific survival (DSS) in OPSCC according to keratinization. Univariate and multivariate survival analyses were performed to estimate survival according to histopathologic profile and smoking status.
  
  
  RESULTS
  In the 208 samples, 96 were keratinizing and 112 were nonkeratinizing. Patients with keratinizing tumors were more likely to have advanced-stage disease and be p16 negative. Keratinization was independently associated with adverse outcomes. The 5-year DSS was significantly higher for nonkeratinizing tumors (63.3%) compared with keratinizing tumors (44.8%; P = .007). In subgroup analysis, nonkeratinization was associated with improved DSS in those with nonbasaloid and p16-negative tumors and in patients who were smokers. When stratifying patients based on keratinization, p16-status, and smoking status, patients with p16-negative keratinizing tumors who were smokers had the lowest 5-year DSS (26.7%).
  
  
  CONCLUSIONS
  Patients with nonkeratinized OPSCC have improved survival compared with those with keratinizing tumors. Information on keratinization is most useful prognostically in those who have p16-negative and nonbasaloid tumors and in patients who are smokers. Survival can be stratified using keratinization, p16 status, and smoking status.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cooper
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Biron
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: Ben
authors.initials: B
authors.lastname: Adam
authors.affiliation: Department of Oncology, University of Calgary, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Klimowicz
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Puttagunta
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada.
authors.forename: Hadi
authors.initials: H
authors.lastname: Seikaly
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D012907:Smoking / Q000401:mortality
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins