bcl-2 immunoreactivity but not p53 accumulation associated with tumour response to radiotherapy in cervical carcinoma

J Cancer Res Clin Oncol. 1999;125(1):55-60. doi: 10.1007/s004320050242.

Abstract

Purpose: This study seeks to define the role of pretreatment expression of the tumour-suppressor p53 protein and the anti-apoptotic protein bcl-2 and their relationship to tumour response to radiotherapy in cervical carcinoma.

Methods: A total of 101 patients were evaluated and the possibility of a correlation done between the pretreatment status of the two proteins and clinical outcome following radiotherapy was investigated. Such patients were either disease-free (group 1, n = 65) or had residual/recurrent disease (group 2, n = 36) at a 16-month follow-up. p53 and bcl-2 protein expression was determined by immunocytochemistry. The presence of mutant p53 was detected by a mutant specific p53 enzyme-linked immunosorbent assay.

Results: There was no correlation between p53 immunoreactivity or the presence of mutant p53 protein and disease status after treatment. Expression of bcl-2 protein, however, showed significant pretreatment correlations with the final disease outcome (r = 0.643, P = 0.0001). Moreover the odds ratio of a tumour expressing moderate to intense levels of bcl-2 responding poorly to radiotherapy was 27.2 (95% CI 6.0, 123.3).

Conclusions: bcl-2 protein functions in an anti-oxidant pathway to prevent apoptosis. Since radiotherapy efficacy depends on adequate DNA damage caused by free-radical generation, increased expression of bcl-2 may result in tumours becoming less responsive to radiation. Mutation of the p53 gene, however, is a rare event in cervical cancer. Since bcl-2 is negatively regulated by p53, it could be presumed that the p53 detected in the tumour cells may be non-functional or inactive possibly because of interaction with proteins such as E6 or mdm-2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / chemistry
  • Cytoplasm / chemistry
  • Disease-Free Survival
  • Female
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local
  • Neoplasm, Residual
  • Odds Ratio
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / analysis*
  • Uterine Cervical Neoplasms / chemistry
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53