TP53, BCL-2 and BAX analysis in 199 ovarian cancer patients treated with taxane-platinum regimens

Gynecol Oncol. 2009 Jan;112(1):179-84. doi: 10.1016/j.ygyno.2008.09.008. Epub 2008 Oct 19.

Abstract

Objective: In cell line studies, BCL-2 and BAX proteins interfere with cancer response to taxanes. This issue has not received much attention with regard to taxane-platinum (TP)-treated ovarian cancer patients.

Methods: We evaluated prognostic/predictive significance of BCL-2 and BAX with regard to TP53 status. Immunohistochemical analysis was performed on 199 ovarian carcinomas FIGO stage IIB-IV treated with TP; the results were analyzed by the Cox and logistic regression models.

Results: Clinicopathological parameters (residual tumor size, FIGO stage and/or tumor grade, but not patient's age) were the only or the strongest predictors of patient's outcome. Platinum highly sensitive response showed a positive association with TP53 accumulation (p=0.045). As in our previously published analysis on platinum-cyclophosphamide-treated group, complete remission showed a borderline negative (paradoxic) association with high BAX expression in the whole group (p=0.058) and with BCL-2 expression in the TP53(-) group (p=0.058).

Conclusion: Our results suggest that TP53, BCL-2 and BAX proteins carry some predictive potential in taxane-platinum-treated ovarian cancer patients, auxiliary to clinicopathological factors. We have confirmed on another patient group that clinical importance of BCL-2 may depend on TP53 status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Docetaxel
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Taxoids / administration & dosage
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Young Adult
  • bcl-2-Associated X Protein / biosynthesis*

Substances

  • BAX protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Taxoids
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Docetaxel
  • Carboplatin
  • Paclitaxel
  • Cisplatin