title: Alterations of Smad expression and activation in defining 2 subtypes of human head and neck squamous cell carcinoma.
abstract: BACKGROUND
  We postulated that disruptions of the canonical transforming growth factor-beta (TGF-β)/Smad signaling pathway might contribute to the development of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  A cohort of 798 HNSCC tumor samples from 346 patients were analyzed by immunohistochemistry (IHC) to define the pattern of expression of (phospho)Smad2, (phospho)Smad3, and Smad4.
  
  
  RESULTS
  We found that 19%, 40%, and 12% of HNSCC specimens failed to express pSmad2, pSmad3, or Smad4, respectively. Loss of Smad2/3 activation was observed in 8.5% of specimens. In addition, 4% of specimens failed to express only Smad4. Moreover, patients with pSmad2/3-negative tumors had a significantly better overall survival than that of those whose tumors expressed activated Smad2/3. In contrast, loss of Smad4 expression did not have prognostic significance.
  
  
  CONCLUSIONS
  Our results indicate that HNSCC in which Smad2/3 are inactivated or in which Smad4 expression is lost represent 2 distinct tumor subtypes with different clinical outcomes.
authors.affiliation: Department of Internal Medicine, UMDNJ-Robert Wood Johnson Medical School, Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.forename: Seena
authors.initials: S
authors.lastname: Aisner
authors.forename: Soly
authors.initials: S
authors.lastname: Baredes
authors.forename: Gangadhar
authors.initials: G
authors.lastname: Sreepada
authors.forename: Rasesh
authors.initials: R
authors.lastname: Shah
authors.forename: Michael
authors.initials: M
authors.lastname: Reiss
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015398:Signal Transduction; D051785:Smad Proteins / Q000096:biosynthesis*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta