title: Aberrant expression of p-Smad3 in oral carcinogenesis.
abstract: OBJECTIVE
  Smads are the keys of transforming growth factor β (TGFβ) signaling cascade and play a crucial role in many cancers. Once TGFβ receptors are activated, Smad2 and Smad3 are phosphorylated and form complexes with Smad4. These complexes translocate from the cytoplasm to the nucleus where they regulate the target genes. The subcellular localization of phosphorylated Smad3 (p-Smad3) in oral carcinogenesis has never been reported. This study investigated the subcellular distribution of p-Smad3 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL) with and without dysplasia.
  
  
  METHODS
  Expression of p-Smad3 was immunohistochemically examined in 150 samples including OSCC, OL with and without dysplasia, and normal mucosa (NM). Cytoplasmic and nuclear positive cells were counted separately. The results were present as the frequency of positive cases.
  
  
  RESULTS
  Cytoplasmic and/or nuclear staining for p-Smad3 was detected. The frequency of cytoplasmic expression in OL with dysplasia was significantly higher than that in NM. The numbers of cytoplasmic expression and cytoplasmic plus nuclear expression in OSCC were significantly higher than those in NM and OL with and without dysplasia.
  
  
  CONCLUSIONS
  The overexpression of cytoplasmic p-Smad3 in OL with dysplasia and in OSCC suggests that p-Smad3 is in the nonfunctional state. Thus, the growth inhibitory effect of p-Smad3 is diminished during oral carcinogenesis. The cytoplasmic plus nuclear staining of p-Smad3 was aberrant in OSCC.
  
  
  CONCLUSIONS
  The cytoplasmic staining of p-Smad3 may serve as a marker for oral premalignant lesions whereas the cytoplasmic plus nuclear staining of p-Smad3 may serve as a marker for OSCC.
authors.affiliation: Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Yothi Street, Bangkok, 10400, Thailand, spoomsawat@yahoo.com.
authors.forename: Sopee
authors.initials: S
authors.lastname: Poomsawat
authors.forename: Jirapa
authors.initials: J
authors.lastname: Punyasingh
authors.forename: Paisarn
authors.initials: P
authors.lastname: Vejchapipat
mesh_terms: D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007972:Leukoplakia, Oral / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D051900:Smad3 Protein / Q000378:metabolism*
chemical_list: C497790:SMAD3 protein, human; D051900:Smad3 Protein