Publication

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

Leffers, N., Lambeck, A. J. A., de Graeff, P., Bijlsma, A. Y., Daemen, T., van der Zee, A. G. J. & Nijman, H. W., Sep-2008, In : Gynecologic Oncology. 110, 3, p. 365-373 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

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 1 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

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. (C) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)365-373
Number of pages9
JournalGynecologic Oncology
Volume110
Issue number3
Publication statusPublished - Sep-2008

    Keywords

  • p53, MHC class I, ovarian cancer, immune escape, p53 autoantibodies, T-CELL RESPONSES, COLORECTAL-CANCER, CLINICAL-SIGNIFICANCE, PROGNOSTIC-FACTOR, ESCAPE MECHANISM, DISEASE STAGE, LUNG-CANCER, PHASE-I, EXPRESSION, CARCINOMA

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