Δ133p53 is an independent prognostic marker in p53 mutant advanced serous ovarian cancer

• Published in: British journal of cancer Vol. 105; no. 10; pp. 1593 - 1599
• Main Authors: Hofstetter, G, Berger, A, Schuster, E, Wolf, A, Hager, G, Vergote, I, Cadron, I, Sehouli, J, Braicu, E I, Mahner, S, Speiser, P, Marth, C, Zeimet, A G, Ulmer, H, Zeillinger, R, Concin, N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.11.2011; Nature Publishing Group
• Subjects: 692/53/2422; 692/699/67/1517/1709; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Female; Genes, p53; Humans; Middle Aged; Molecular Diagnostics; Molecular Medicine; Mutation; Oncology; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Prognosis; Prospective Studies; Real-Time Polymerase Chain Reaction; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; p53 isoforms; ovarian cancer; delta133p53; p73; p53
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.433

Background: We aimed to evaluate the clinical relevance of p53 and p73 isoforms that modulate the function of p53. Methods: This prospective multicentre study included 154 patients with stage III and IV serous ovarian cancer. A functional yeast-based assay and subsequent sequencing were performed to analyse the p53 mutational status. Expression of p53 and p73 isoforms was determined using RT–qPCR. Results: Δ133p53 expression constituted an independent prognostic marker for recurrence-free (hazard ratio=0.571, P =0.016, 95% CI: 0.362–0.899) and overall survival (hazard ratio=0.365, P =0.004, 95% CI: 0.182–0.731) in patients with p53 mutant ovarian cancer ( n =121). High Δ40p53 expression was associated with favourable tumour grading ( P =0.037) and improved recurrence-free survival (33.4 vs 19.6 months, P =0.029), but not overall survival (43.1 vs 33.6 months, P =0.139), in patients with p53 wild-type cancer ( n =33). Neither the p53 mutational status nor p73 isoform expression possessed prognostic significance in the examined ovarian cancer cases. Conclusion: Δ133p53 expression was associated with prognosis in the vast majority of ovarian cancer cases, that is, patients with p53 mutant advanced serous carcinomas. Thus, our findings underline the importance of considering the complex p53 regulatory network.