The N-Terminally Truncated p53 Isoform Δ40p53 Influences Prognosis in Mucinous Ovarian Cancer

Objective: The tumor suppressor p53 generates the N-terminally truncated isoforms Delta 40p53 and Delta 133p53 that possess the ability to modulate p53 function in vitro. The aim of the present study was to evaluate the clinical relevance of p53 isoforms in the main histological subtypes of ovarian cancer. Methods: Delta 40p53, Delta 133p53, and full-length p53 (FLp53) expression was determined in 45 mucinous, 30 endometrioid, and 91 serous ovarian cancer specimens as well as 42 normal ovarian tissues using reverse transcriptaseYquantitative polymerase chain reaction. In a subgroup of mucinous ovarian cancer cases, Delta 40p53 expression was examined using Western blot analysis. A functional yeast-based assay and subsequent sequencing were performed to analyze the p53 mutational status. Results: In endometrioid cancer specimens, Delta 133p53 expression was significantly lower than in mucinous and serous cases (P = 0.016) or in normal tissues (P = 0.004). Mucinous cancer samples showed elevated Delta 40p53 expression as compared with normal ovarian tissues (P = 0.003). In addition, high Delta 40p53 expression constituted an independent prognostic marker for recurrence-free but not for overall survival in patients with mucinous ovarian cancer (hazard ratio, 0.267; 95% confidence interval, 0.094-0.756 [P = 0.013]; hazard ratio, 0.453, 95% confidence interval, 0.193-1.064 [P = 0.069]). Western blot analysis confirmed the presence of p53A and Delta 40p53 alpha in a subset of patients with mucinous ovarian cancer. Expression of p53 isoforms was not associated with p53 mutational status or clinicopathologic parameters. Conclusions: We show that expression of p53 isoforms differs in histological subtypes, thus supporting the hypothesis that histological subtypes represent distinct disease entities. In addition, we provide first evidence for a favorable role of Delta 40p53 in patients with mucinous ovarian cancer.