title: Expression of Smad and its signalling cascade in osteosarcoma.
abstract: OBJECTIVE
  Smad signalling is important for inducing the expression of cell cycle inhibitors such as p21/WAF1, thereby facilitating transforming growth factor (TGF)-beta mediated inhibition of cell growth. The role and clinical implications of Smad signalling in osteosarcoma remain unclear.
  
  
  METHODS
  We assessed the immunohistochemical expression profiles of Smad2, P-Smad2, Smad4, and p21/WAF1 proteins in 34 cases of osteosarcoma. We also investigated whether the expression of these proteins was correlated with clinicopathological parameters.
  
  
  RESULTS
  The p21/WAF1 expression showed a significant relationship with tumour extension (p = 0.018). Smad4 expression was significantly correlated with Smad2 (p = 0.019) and P-Smad2 (p = 0.006) expression in osteosarcoma. Kaplan-Meier analysis showed that tumour extension (p = 0.0038), TNM stage (p = 0.0096), and p21/WAF1 expression (p = 0.0023) were significantly correlated with overall survival. Cox multivariate analysis showed that tumour extension (p = 0.048) and p21/WAF1 expression (p = 0.022) were independent poor prognostic factors.
  
  
  CONCLUSIONS
  Smad signalling in osteosarcoma is partially operative. The high p21/WAF1 expression in osteosarcoma is significantly correlated with tumour extension. Our results suggest that overexpression of p21/WAF1 in osteosarcoma might be one of the poor prognostic factors.
authors.affiliation: Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Kyu Yeoun
authors.initials: KY
authors.lastname: Won
authors.forename: Youn Wha
authors.initials: YW
authors.lastname: Kim
authors.forename: Yong-Koo
authors.initials: YK
authors.lastname: Park
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000096:biosynthesis*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051785:Smad Proteins