title: Evaluation of PTEN, PI3K, MTOR, and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma.
abstract: OBJECTIVE
  Important signalling pathways play fundamental roles in the pathogenesis of thyroid carcinoma (TC). PTEN, mTOR, PI3K-p85 and K-Ras are the principal factors involved in these signalling pathways. To immunohistochemically examine the expressions of PI3K, mTOR and PTEN in patients suffering from follicular TC, papillary TC or variants thereof, as well as to investigate KRAS mutations via PCR to determine their clinical and prognostic relevance to differentiated thyroid cancer.
  
  
  METHODS
  The expression of PTEN, PI3K-p85 and mTOR was immunohistochemically examined, and the mutation of K-Ras was examined via PCR. The results obtained were compared to the clinico-pathologic characteristics of the patients.
  
  
  RESULTS
  A significant correlation was found between p85 expression and lymphovascular invasions and between PTEN expression and multifocality (p = 0.048 and p = 0.04, respectively), and a correlation between p85 and capsular invasion was found, with a borderline statistical significance (p = 0.056). No expression of PTEN, p85 or Mtor was detected in normal tissue. K-Ras mutation was examined in 66 of the 101 patients (57.4%), and the percentage of patients exhibiting a K-Ras mutation was 17.4%. All of the patients exhibiting a K-Ras mutation were women (p = 0.047). The disease-free survival was 44.6 months (95% CI: 37.9-51.3) and was statistically significantly higher in the group that displayed level 1 or lower expression of p85 (p = 0.043).
  
  
  CONCLUSIONS
  The expression levels of the aforementioned markers were significantly higher in TC cells than in normal tissue. A significant correlation was detected between K-Ras mutation and gender. This study demonstrates that p85 and PTEN are markers that should be evaluated in further studies of TC.
authors.affiliation: Department of Medical Oncology, Medical Faculty, Cukurova University, Adana, Turkey.
authors.forename: Berna B
authors.initials: BB
authors.lastname: Duman
authors.affiliation: Department of Medical Oncology, Medical Faculty, Cukurova University, Adana, Turkey.
authors.forename: Oğuz I
authors.initials: OI
authors.lastname: Kara
authors.affiliation: Department of Pathology, Medical Faculty, Cukurova University, Adana, Turkey.
authors.forename: Aysum
authors.initials: A
authors.lastname: Uğuz
authors.affiliation: Department of Pathology, Medical Faculty, Cukurova University, Adana, Turkey.
authors.forename: Berna T
authors.initials: BT
authors.lastname: Ates
keywords: K-Ras; PI3K; PTEN; mTOR; thyroid cancer