title: Combined cytoplasmic and membranous EGFR and p53 overexpression is a poor prognostic marker in early stage oral squamous cell carcinoma.
abstract: OBJECTIVE
  Our aim was to evaluate the expression of several molecules that regulate growth, the cell cycle and signalling pathways including EGFR, p53, p16 and p27 in oral squamous cell carcinomas (OSCC). We examined their utility as prognostic markers by relating to clinicopathological characteristics and the clinical outcome.
  
  
  METHODS
  Using tissue microarray technology, we analysed 67 primary OSCC and examined immunohistochemical expression of EGFR, p53, p16 and p27. Multivariate analysis was conducted to examine their role in survival.
  
  
  RESULTS
  Many of the markers were highly expressed in these cancers. Membranous EGFR expression in 95.2%, both membrane and cytoplasm expression in 35%, p53 expression in 61.6%, p27 expression in 89.5% and p16 expression in 27.9% of cases. In the multivariate analysis, independent prognostic influence of a lower overall survival was determined only for advanced tumour stage (P < 0.001), p53 overexpression (P = 0.004), EGFR cytoplasm and membrane co-expression location (P = 0.002) and p16 reduced expression (P = 0.002). When considering a subgroup of early stage tumours, p53 overexpression (P = 0.028) and combined membranous and cytoplasm EGFR co-expression (P = 0.039) were indicators of a lower overall survival. For disease-free survival, in addition to these three factors, the histological grade (P = 0.011) showed independent prognostic values.
  
  
  CONCLUSIONS
  The independent value of EGFR subcellular location (cytoplasm and membrane) and p53 overexpression in overall survival even in early stages of OSCC suggests that these markers may serve as reliable biological markers to identify high-risk subgroups and to guide therapy.
authors.affiliation: Medicine and Oral Surgery Department, Dental Sciences Group-Health Sciences Research Centre, Instituto Superior de Ciências da Saúde Norte, Paredes, Portugal. lmonteiro.md@gmail.com
authors.forename: Luís Silva
authors.initials: LS
authors.lastname: Monteiro
authors.forename: Márcio
authors.initials: M
authors.lastname: Diniz-Freitas
authors.forename: Tomás
authors.initials: T
authors.lastname: Garcia-Caballero
authors.forename: Saman
authors.initials: S
authors.lastname: Warnakulasuriya
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Forteza
authors.forename: Máximo
authors.initials: M
authors.lastname: Fraga
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen; D066246:ErbB Receptors