Expression of Bcl-2 and the antiapoptotic BAG family proteins in ovarian cancer

Appl Immunohistochem Mol Morphol. 2013 Dec;21(6):518-24. doi: 10.1097/PAI.0b013e318284a053.

Abstract

In epithelial ovarian cancer (EOC), literature on the prognostic value of B-cell lymphoma 2 (Bcl-2) is limited and inconsistent. Little is known about the expression patterns and the prognostic value of prosurvival proteins of the Bcl-2-associated athanogene (BAG) family proteins interacting with Bcl-2. The major aim of this study was to further define the expression pattern and the prognostic role of Bcl-2 together with BAG-1, BAG-3, and BAG-4 proteins in EOC patients receiving platinum/taxane-based chemotherapy. A tissue array was constructed comprising 63 EOC patients. The expression and the prognostic value of Bcl-2, BAG-1, BAG-3, and BAG-4 in EOC were evaluated by immunohistochemistry and multivariate analysis. A positive cytoplasmic staining for Bcl-2 was observed in 23.8% of EOC samples and in all histologic subtypes. BAG-1, BAG-3, and BAG-4 were detected in tumor cell nuclei and cytoplasm. Interestingly, all patients presenting with a positive Bcl-2 staining showed additional positive nuclear and cytoplasmic BAG-4 expression (P=0.014). Expression of Bcl-2, or the BAG family proteins, independent of nuclear or cytoplasmic localization, had no significant impact on either disease-free or overall survival, both in univariate and multivariate survival analyses with the limitation of a small cohort of cases. In this study, no association between Bcl-2 expression in EOC tumor tissue and prognosis was found. Similarly, nuclear and cytoplasmic expression of the prosurvival proteins of the BAG family had no significant impact on patients' outcome.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Apoptosis Regulatory Proteins / genetics*
  • Bridged-Ring Compounds / therapeutic use
  • Carcinoma, Ovarian Epithelial
  • DNA-Binding Proteins / genetics*
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Platinum / therapeutic use
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Survival Analysis
  • Taxoids / therapeutic use
  • Transcription Factors / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BAG3 protein, human
  • BAG4 protein, human
  • BCL2-associated athanogene 1 protein
  • Bridged-Ring Compounds
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Taxoids
  • Transcription Factors
  • taxane
  • Platinum