Survival of ovarian cancer patients overexpressing the tumour antigen p53 is diminished in case of MHC class I down-regulation

Gynecol Oncol. 2008 Sep;110(3):365-73. doi: 10.1016/j.ygyno.2008.04.043. Epub 2008 Jun 20.

Abstract

Objectives: The adaptive immune system seems to play an essential role in the natural course of ovarian cancer. Aim of this study was to establish whether disease-specific survival for patients expressing the tumour antigen p53 is influenced by MHC class I expression or the presence of p53 autoantibodies (p53-Aab).

Methods: P53 and MHC class I expression were analysed in ovarian cancer tissue of 329 patients by immunohistochemistry using tissue microarrays. For 233 patients, pre-treatment serum samples were available to study the presence of p53 autoantibodies by ELISA. Data were linked to clinicopathological parameters and disease-specific survival.

Results: P53 overexpression, MHC class I down-regulation in neoplastic cells and serum p53 autoantibodies were observed in 49.4, 38.9 and 15.9% of patients, respectively. MHC class I down-regulation in p53-overexpressing tumours correlated with a 10-month reduced disease-specific survival in univariate analysis (log-rank 4.10; p=0.043). p53-Aab were strongly correlated with p53 overexpression (p<0.001), but did not influence disease-specific survival.

Conclusions: As the prognosis of patients with p53-overexpressing ovarian cancer is affected by the MHC class I status of tumour cells and ovarian cancer patients can generate immune responses to the p53 tumour antigen, the further development of immunotherapy should evaluate strategies to improve MHC class I expression by tumour cells to facilitate antigen presentation in an attempt to increase clinical responses.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / biosynthesis
  • Autoantibodies / immunology
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Survival Rate
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Tumor Suppressor Protein p53 / immunology

Substances

  • Autoantibodies
  • Histocompatibility Antigens Class I
  • TP53 protein, human
  • Tumor Suppressor Protein p53