title: Tissue microarray evidence of association between p16 and phosphorylated eIF4E in tonsillar squamous cell carcinoma.
abstract: BACKGROUND
  Expression of p16 is a marker for human papillomavirus (HPV)-related carcinogenesis in head and neck cancer. The purpose of this study is to determine if p16 immunoreactivity is associated with aberrant expression of components of the PI3 kinase pathway.
  
  
  METHODS
  A tissue microarray (TMA) was constructed for 46 archived tonsillar squamous cell carcinoma specimens. Clinical demographics of these patients were analyzed, and the TMA was interrogated with antibodies directed against p16, phosphorylated Akt(Ser473), phosphorylated S6(Ser240/244), phosphorylated S6(Ser235/236), phosphorylated 4E-BP1(Thr37/46), phosphorylated eIF4E(Ser209), PTEN, p21, and p53.
  
  
  RESULTS
  There was a significant correlation between history of tobacco abuse (>10 pack/years) and absence of p16 expression (p = .01). Expression of p16 was significantly associated with immunoreactivity of p21 (p = .02), PTEN (p = .02), and phosphorylated eIF4E (p = .03). There was no evidence of association between p16 status and expression of phosphorylated S6, phosphorylated 4E-BP1, or p53.
  
  
  CONCLUSIONS
  p16 positive tonsillar squamous cell carcinoma is characterized by expression of phosphorylated eIF4E that may occur via a mammalian target of rapamycin (mTOR)-independent mechanism.
authors.affiliation: Head and Neck Medical Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. furym@mskcc.org
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Fury
authors.forename: Marija
authors.initials: M
authors.lastname: Drobnjak
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Marina
authors.initials: M
authors.lastname: Asher
authors.forename: Jatin
authors.initials: J
authors.lastname: Shah
authors.forename: Nancy
authors.initials: N
authors.lastname: Lee
authors.forename: Diane
authors.initials: D
authors.lastname: Carlson
authors.forename: H Guido
authors.initials: HG
authors.lastname: Wendel
authors.forename: David G
authors.initials: DG
authors.lastname: Pfister
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D012189:Retrospective Studies; D012907:Smoking / Q000453:epidemiology; D046888:Tissue Array Analysis; D014067:Tonsillar Neoplasms / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D039561:Eukaryotic Initiation Factor-4E; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human