title: Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma.
abstract: BACKGROUND
  The objective of this study was to link expression patterns of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC).
  
  
  METHODS
  Expression levels of Bmi-1 and p16 in samples from 252 patients with OSCC were evaluated immunohistochemically using the tissue microarray method. Staining intensity was determined by calculating an intensity reactivity score (IRS). Staining intensity and the localization of expression within tumor cells (nuclear or cytoplasmic) were correlated with overall, disease-specific, and recurrence-free survival.
  
  
  RESULTS
  The majority of cancers were localized in the oropharynx (61.1%). In univariate analysis, patients who had OSCC and strong Bmi-1 expression (IRS >10) had worse outcomes compared with patients who had low and moderate Bmi-1 expression (P = .008; hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.167-2.838); this correlation was also observed for atypical cytoplasmic Bmi-1 expression (P = .001; HR, 2.164; 95% CI, 1.389-3.371) and for negative p16 expression (P < .001; HR, 0.292; 95% CI, 0.178-0.477). The combination of both markers, as anticipated, had an even stronger correlation with overall survival (P < .001; HR, 8.485; 95% CI, 4.237-16.994). Multivariate analysis demonstrated significant results for patients with oropharyngeal cancers, but not for patients with oral cavity tumors: Tumor classification (P = .011; HR, 1.838; 95%CI, 1.146-2.947) and the combined marker expression patterns (P < .001; HR, 6.254; 95% CI, 2.869-13.635) were correlated with overall survival, disease-specific survival (tumor classification: P = .002; HR, 2.807; 95% CI, 1.477-5.334; combined markers: P = .002; HR, 5.386; 95% CI, 1.850-15.679), and the combined markers also were correlated with recurrence-free survival (P = .001; HR, 8.943; 95% CI, 2.562-31.220).
  
  
  CONCLUSIONS
  Cytoplasmic Bmi-1 expression, an absence of p16 expression, and especially the combination of those 2 predictive markers were correlated negatively with disease-specific and recurrence-free survival in patients with oropharyngeal cancer. Therefore, the current results indicate that these may be applicable as predictive markers in combination with other factors to select patients for more aggressive treatment and follow-up.
authors: Otorhinolaryngology, Head and Neck Surgery, University Hospital of Zurich, Switzerland. gerry.huber@usz.ch
authors: Gerhard F
authors: GF
authors: Huber
authors: Andrea
authors: A
authors: Albinger-Hegyi
authors: Alex
authors: A
authors: Soltermann
authors: Matthias
authors: M
authors: Roessle
authors: Nicole
authors: N
authors: Graf
authors: Stephan K
authors: SK
authors: Haerle
authors: David
authors: D
authors: Holzmann
authors: Holger
authors: H
authors: Moch
authors: Ivan
authors: I
authors: Hegyi
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C489421:Bmi1 protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011518:Proto-Oncogene Proteins; D063150:Polycomb Repressive Complex 1