PURPOSE: We aimed to determine the clinical role of the p53 family members p53 
and p73 in the responsiveness to platinum-based chemotherapy and survival in 
ovarian cancer, considering their cross-talk and the p53 polymorphism at codon 
72.
EXPERIMENTAL DESIGN: A detailed analysis of p53 and p73 in a series of 122 
ovarian cancers was done. We used a functional yeast-based assay to determine 
the p53 mutational status. Red yeast colonies, indicating mutant p53, were 
subsequently sequenced to determine the specific p53 alteration. p53 mutations 
were divided into two groups according to their previous characterization in the 
literature: those that efficiently inhibit transcriptionally active TAp73 
function and those that do not. A p53 polymorphism at codon 72 was determined in 
corresponding normal tissue or blood of ovarian cancer patients. 
Isoform-specific p73 expression analysis using real-time reverse 
transcription-PCR has previously been done in the majority of ovarian cancers 
included in this study. In a retrospective chart review, responsiveness to 
chemotherapy was assessed, and survival data with long follow-up times were 
collected.
RESULTS: Eighty of 122 (65.6%) of ovarian cancers harbored p53 mutations. p53 
mutational status was an important determinant of responsiveness to 
platinum-based chemotherapy in all patients with a residual tumor of <2 cm in 
diameter after initial surgery (wild-type versus mutant, P = 0.029). In 
addition, p53 mutational status was a strong prognosticator for recurrence-free 
and overall survival (P < 0.0001 and P = 0.003, respectively) in univariate 
analyses. High expression levels of dominant-negative p73 isoforms (DeltaNp73 
and DeltaN'p73) significantly correlated with chemotherapeutic failure (P = 
0.048) and with worse recurrence-free and overall survival in patients with p53 
mutant cancers (P = 0.048 and P = 0.005, respectively). Eight p53 mutations, 
present in 19 cases, were found that efficiently inhibit TAp73 (i.e., 175H, 
220C, 245S, 245D, 248W, 248Q, 266E, and 273H). Patients with p53 mutations that 
efficiently inhibit TAp73 function had a significantly shorter overall survival 
than patients with p53 mutations of unknown effect on TAp73 (P = 0.044). The p53 
polymorphism at codon 72 had no influence on responsiveness to chemotherapy or 
survival.
CONCLUSION: We provide the first clinical evidence that dominant-negative p73 
isoforms contribute to drug resistance in vivo, underscoring the importance of a 
p53-p73 cross-talk. NH2-terminally truncated p73 isoforms were of significant 
clinical effect by providing an additional unfavorable factor for response to 
platinum-based chemotherapy and survival in p53 mutant ovarian cancers.