title: PI3K-AKT-mTOR pathway proteins are differently expressed in oral carcinogenesis.
abstract: BACKGROUND
  PI3K-AKT-mTOR signaling pathway is associated with several cellular functions and is frequently changed in several malignancies. The aim of this study was to characterize the immunohistochemical expression pattern of components in PI3K-AKT-mTOR signaling pathway in oral epithelial dysplasia (OED), comparing to oral squamous cell carcinoma (OSCC) and non-dysplastic oral tissues (NDOT).
  
  
  METHODS
  A total of 186 cases of NDOT, OED and OSCC were retrieved. Nuclear staining and cytoplasmic staining of the keratinocytes were considered positive, and the percentage of positive cells was calculated.
  
  
  RESULTS
  Increased immunoreactivity from NDOT to OED and OSCC was seen for all proteins. In NDOT cases, positivity was found only for pS6 (52.9%) and p4EBP1 (13.5%). In OED, immunoreactivity was observed for pAKT (62.2%), pmTOR (28.6%), pS6 (70.8%), and p4EBP1 (42.9%). In OSCC cases, immunoreactivity was found for pAKT (83.3%), pmTOR (50%), pS6 (77.4%), and p4EBP1 (50%). The pAKT and pmTOR expression was higher in OED (<0.001, Fisher's exact test) and OSCC (<0.001, Fisher's exact test).
  
  
  CONCLUSIONS
  Our study demonstrated higher pAKT and pmTOR expression during carcinogenesis of oral mucosa, differing considerably among OED and OSCC specimens when compared to NDOT. These proteins can be considered potential diagnostic markers for early detection of cancer.
authors.affiliation: Department of Oral Pathology, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil. fabmm@usp.br.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Martins
authors.affiliation: Department of Oral Pathology, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Suzana Com
authors.initials: SC
authors.lastname: de Sousa
authors.affiliation: Department of Oral Pathology, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dos Santos
authors.affiliation: Oral Medicine Infection and Immunity, Advanced Graduate Education Program in Oral and Maxillofacial Pathology, Division of Oral Medicine and Dentistry, Brigham and Women's Hospital, Boston, MA, US.
authors.forename: Sook-Bin
authors.initials: SB
authors.lastname: Woo
authors.affiliation: Department of Oral Pathology, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: Gallottini
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D002278:Carcinoma in Situ / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011230:Precancerous Conditions / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: PI3K-AKT-mTOR pathway; oral cancer; oral epithelial dysplasia; p4EBP1; pS6