title: Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia.
abstract: BACKGROUND
  Prognostic biomarkers aim to improve on the current inadequate method of histological assessment to identify patients with oral epithelial dysplasia at greatest risk of malignant transformation. We aimed to assess the prognostic ability of six protein biomarkers linked to the epidermal growth factor receptor (EGFR) pathway, including three tetraspanins, in a large multicentre oral dysplasia cohort.
  
  
  METHODS
  One hundred and forty-eight cases with varying degrees of epithelial dysplasia underwent immunohistochemical assessment for CD9, CD151, CD82, EGFR, Her-2, and COX-2. Scoring was performed independently by two observers. Univariate analyses using both logistic and Cox regression models and a multivariate regression were performed.
  
  
  RESULTS
  Malignant progression was significantly greater in those cases with decreased expression of CD9 (P=0.02), and increased expression of CD151 (P=0.02), EGFR (P=0.04), and COX-2 (P=0.003). Histological grade (P=0.0002) and morphology (P=0.03) were also prognostic, whereas smoking and alcohol were not. The optimal combination by backward-variable selection was of histological grade (hazard ratio (HR) 1.64; 95% CI 1.12, 2.40), COX-2 overexpression (HR 1.12; 1.02, 1.24) and CD9 underexpression (HR 0.88; 0.80, 0.97). CD82 and Her-2 demonstrated no prognostic ability.
  
  
  CONCLUSIONS
  This is the first study of the expression and prognostic potential of the tetraspanins in oral dysplasia. A combination of certain biomarkers with clinical factors appeared to improve the accuracy of determining the risk of malignancy in individuals with oral dysplasia. These findings may also offer potential new therapeutic approaches for this condition.
authors.affiliation: 1] Institute of Head and Neck Studies and Education (InHANSE), School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK [2] Department of Otolaryngology, University Hospital Coventry and Warwickshire, Coventry CV2 2DX, UK [3] Department of Otolaryngology, University Hospital Birmingham, Birmingham B15 2WB, UK.
authors.forename: P
authors.initials: P
authors.lastname: Nankivell
authors.forename: H
authors.initials: H
authors.lastname: Williams
authors.forename: C
authors.initials: C
authors.lastname: McConkey
authors.forename: K
authors.initials: K
authors.lastname: Webster
authors.forename: A
authors.initials: A
authors.lastname: High
authors.forename: K
authors.initials: K
authors.lastname: MacLennan
authors.forename: B
authors.initials: B
authors.lastname: Senguven
authors.forename: P
authors.initials: P
authors.lastname: Rabbitts
authors.forename: H
authors.initials: H
authors.lastname: Mehanna
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000378:metabolism; D011230:Precancerous Conditions / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D060185:Tetraspanin 24 / Q000378:metabolism*; D060245:Tetraspanin 29 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C554715:CD151 protein, human; C554869:CD9 protein, human; D060185:Tetraspanin 24; D060245:Tetraspanin 29; D051546:Cyclooxygenase 2; D066246:ErbB Receptors