title: Mitogen-activated protein kinase pathway in osteosarcoma.
abstract: OBJECTIVE
  The MAPK pathway has been shown to contribute to the prognostic role and drug resistance in many cancers. In addition, the MAPK pathway was found to play a role in the aggressive behaviour of osteosarcoma (OS). We hypothesised that the expression of the MAPK pathway components may be of value in predicting the prognosis of patients with OS.
  
  
  METHODS
  We evaluated the expression of pan-Ras, Raf-1, pMEK1/2 and pERK1/2 in 61 OS samples using immunohistochemistry and evaluated their effect on event free survival (EFS) and overall survival (OVS).
  
  
  RESULTS
  pan-Ras, Raf-1, pMEK1/2 and pERK1/2 were found to be expressed in seven (11%), 36 (59%), 36 (59%) and 30 (49%) of 61 samples, respectively. Patients groups whose tumours expressed Raf-1, pMEK1/2 or pERK1/2 had a poorer clinical outcome than the group whose tumours did not express those antibodies. In addition, positive pMEK1/2 expression was associated with shorter EFS and OVS, irrespective of other prognostic factors.
  
  
  CONCLUSIONS
  Our results further support the findings that aberrant expression of the MAPK pathway components may be the underlying mechanism behind OS, which results in more aggressive clinical behaviour. Furthermore, there may be a decrease in EFS and OVS in OS patients who have tumours that stain positively for pMEK.
authors.affiliation: Department of Pathology, Graduate School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Ki Yong
authors.initials: KY
authors.lastname: Na
authors.forename: Youn Wha
authors.initials: YW
authors.lastname: Kim
authors.forename: Yong-Koo
authors.initials: YK
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality; D002648:Child; D005260:Female; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality; D010766:Phosphorylation; D011379:Prognosis; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: C482128:MAP2K2 protein, human; D019908:Proto-Oncogene Proteins c-raf; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D018631:ras Proteins