Survival of ovarian cancer patients overexpressing the tumour antigen p53 is diminished in case of MHC class I down-regulation.
OBJECTIVE
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.
Gynaecological Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ninke
N
Leffers
Annechien J A
AJ
Lambeck
Pauline
P
de Graeff
Astrid Y
AY
Bijlsma
Toos
T
Daemen
Ate G J
AG
van der Zee
Hans W
HW
Nijman
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000276:immunology
D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53