title: Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma.
abstract: OBJECTIVE
  To investigate the immunohistochemical expression of three apoptosis-related genes (bax, bcl-2, and p53) and apoptosis (TUNEL) in patients with primary osteosarcoma, and examine potential correlations between gene expression and clinicopathological characteristics in these patients.
  
  
  METHODS
  Thirty-five primary osteosarcoma specimens and 18 tissue specimens deriving from non-malignant osseous lesions were immunohistochemically stained for bax, bcl-2, and p53 proteins, while apoptosis was investigated by the TUNEL method. The results were statistically analyzed.
  
  
  RESULTS
  P53, bax, and bcl-2 protein expression was observed in 22 (62.9%), 29 (82.9%), and 18 (51.4%) osteosarcoma patients, respectively. Non-specific positive TUNEL staining (+/-) was observed in two primary osteosarcoma cases (5.7%). None of the benign controls expressed any of the genes studied. None of the apoptosis-related genes studied was able to predict overall or disease-free survival in our group of patients. Nevertheless, increased bax/bcl-2 protein expression ratio was associated with a decreased 4-year survival and disease free survival (P = 0.0229 and P = 0.0370, respectively). Furthermore, all the patients who were bax(+)/bcl-2(-)/p53(+) relapsed within the 4-year follow-up period (P = 0.0385).
  
  
  CONCLUSIONS
  The increased apoptotic rate as determined by an elevated bax/bcl-2 protein expression ratio or by the bax(+)/bcl-2(-)/p53(+) protein expression pattern, appears to identify groups of osteosarcoma patients with unfavorable prognosis.
authors.affiliation: First Department of Orthopaedic Surgery, KAT Hospital, University of Athens, Athens, Greece. labsures@med.uoa.gr
authors.forename: Maria-Kyriaki A
authors.initials: MK
authors.lastname: Kaseta
authors.forename: Lubna
authors.initials: L
authors.lastname: Khaldi
authors.forename: Ilias P
authors.initials: IP
authors.lastname: Gomatos
authors.forename: George P
authors.initials: GP
authors.lastname: Tzagarakis
authors.forename: Leonidas
authors.initials: L
authors.lastname: Alevizos
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Leandros
authors.forename: Panayiotis J
authors.initials: PJ
authors.lastname: Papagelopoulos
authors.forename: Panayiotis N
authors.initials: PN
authors.lastname: Soucacos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein