Prognostic value of bax, bcl-2, and p53 staining in primary osteosarcoma

J Surg Oncol. 2008 Mar 1;97(3):259-66. doi: 10.1002/jso.20913.

Abstract

Background and objectives: 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.

Materials and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis / physiology
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / therapy
  • Female
  • Follow-Up Studies
  • Humans
  • In Situ Nick-End Labeling
  • Male
  • Middle Aged
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Osteosarcoma / therapy
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / metabolism*
  • bcl-2-Associated X Protein / metabolism*

Substances

  • BAX protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein