title: Prognostic utility of basaloid differentiation in oropharyngeal cancer.
abstract: BACKGROUND
  Human papillomavirus (HPV) is recognized as the key risk factor for a distinct subset of oropharyngeal squamous cell carcinoma. P16 is a reliable, sensitive surrogate marker for HPV and confers a positive prognostic advantage. Basaloid differentiation on hematoxylin and eosin (H&E) staining is anecdotally noted by some pathologists to be associated with p16 positivity. This association, however, has not been adequately quantified in the literature, nor has the prognostic implications of basaloid differentiation been described.
  
  
  OBJECTIVE
  1) To correlate the H&E staining feature of basaloid differentiation with p16 positivity in oropharyngeal cancer. 2) To investigate the prognostic utility of basaloid differentiation in oropharyngeal cancer survival.
  
  
  METHODS
  Retrospective cross-sectional study of all patients diagnosed with and treated for oropharyngeal cancer at a single tertiary cancer center from 2002 to 2009. Tissue microarrays (TMAs) were generated from 208 oropharyngeal tumor specimens stained with H&E and immunohistochemical markers. These oropharyngeal TMAs were utilized in several previous publications. Samples were scored for basaloid differentiation by a pathologist blinded to the p16 result. A multivariate survival analysis with Cox-regression and Kaplan-Meier survival analysis was performed.
  
  
  RESULTS
  In the 208 samples, basaloid differentiation correlated with p16 positivity (Spearman's rho 0.435). Basaloid differentiation and p16 positivity were both independent predictors of improved survival. The 5 year disease specific survival (DSS) was 73% for p16 positive tumors and 35% for p16 negative tumors (p < 0.001). Similarly, the 5 year DSS of basaloid differentiated tumors was 74% compared to 41% for non-basaloid tumors (p = 0.001). Patients with p16 positive and basaloid differentiated tumors had the best survival outcomes with a 5 year DSS of 80%.
  
  
  CONCLUSIONS
  Basaloid differentiation is a feature on H&E which correlates with p16 positivity and is a simple, inexpensive, independent, positive prognostic indicator of comparable magnitude to p16 status. Due to the added prognostic value of basaloid differentiation, this feature should be routinely reported by qualified pathologists.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cooper
authors.forename: Vincent
authors.initials: V
authors.lastname: Biron
authors.forename: Ben
authors.initials: B
authors.lastname: Adam
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Klimowicz
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Puttagunta
authors.affiliation: Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Alberta, 1E4 University of Alberta Hospital, Edmonton, AB T6G 2B7, Canada. hadi.seikaly@albertahealthservices.ca.
authors.forename: Hadi
authors.initials: H
authors.lastname: Seikaly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000821:virology; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000821:virology; D052162:Human papillomavirus 16 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000821:virology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D009856:Oncogene Proteins, Viral