title: Smad3 and phospho-Smad3 are potential markers of invasive nonfunctioning pituitary adenomas.
abstract: BACKGROUND
  Transforming growth factor-β (TGF-β) signaling plays important roles in tumor development. Nevertheless, the roles of TGF-β/Smad signaling in nonfunctioning pituitary adenomas (NFPAs) have not been fully studied.
  
  
  METHODS
  Tumor samples were obtained from patients who had NFPAs and underwent endoscopic transsphenoidal surgery or craniotomy at Beijing Tiantan Hospital from March 2008 to December 2012. Immunohistochemistry was performed to determine the expression of Smad transducer proteins in NFPAs. Ki-67 was evaluated as an indicator of the proliferative activity of NFPAs.
  
  
  RESULTS
  A total of 161 patients with NFPAs were identified; 59 (36.6%) had invasive NFPAs and 102 (63.4%) had noninvasive NFPAs. Protein levels of Smad3 and phospho-Smad3 (p-Smad3) were significantly lower in patients with invasive NFPAs than in patients with noninvasive NFPAs (P<0.05 and P<0.01, respectively). The Ki-67 index was markedly greater in invasive NFPAs than in noninvasive NFPAs (P<0.05) and was significant correlated with p-Smad3 levels (P<0.05, r=-0.702).
  
  
  CONCLUSIONS
  A low level of Smad3 and p-Smad3 proteins was associated with the invasion of NFPAs.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China; Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, People's Republic of China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China; Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, People's Republic of China; Department of Neurosurgery, Beijing Tiantan hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Zhenye
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, Beijing Renhe Hospital, Beijing, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China; Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, People's Republic of China; Department of Neurosurgery, Beijing Tiantan hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Chuzhong
authors.initials: C
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China; Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, People's Republic of China; Department of Neurosurgery, Beijing Tiantan hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Zhang
keywords: Ki-67; Smad; invasion; nonfunctioning pituitary adenoma; transforming growth factor-β