p53 protein expression, TP53 gene mutations, and in silico p53 activity as prognostic markers for ovarian cancer

Background: The frequency of alterations in the tumor protein p53 (TP53) gene varies amongs different cancers. Data suggest an overall occurrence rate of 47.8% of TP53 gene alterations in ovarian cancer (OC). This study aimed to investigate the prognostic impact of p53 protein expression, TP53 gene mutations, and in silico prediction of p53 activity. Methods: Blood and tissue samples from 163 OC cases from the Danish Pelvic Mass/Gynecologic Ovarian Vulva Endometrial and Cervix cancer (GOVEC) study were collected through the Danish CancerBiobank (Bio- and GenomeBank, Denmark). We used immunohistochemistry (IHC) to measure p53 protein expression and sequencing, to detect TP53 mutations, and in silico prediction to estimate p53 activity level. Results: p53 protein expression was found to have no prognostic value for overall survival (OS): ≥1%: p = 0.09; ≥10%: p = 0.71. Patients with missense mutations had a shorter OS with a hazard ratio (HR) of 1.80 (95% confidence interval (CI) 1.06–3.04, p = 0.04), while patients with TP53 termination mutation had an even shorter OS with an HR of 2.31 (95% CI 1.13–4.73, p = 0.02). Tissue from 11 patients with positive p53 expression (≥10%) did not have a TP53 mutation in the tumour tissue. The percentage of p53 protein expression positivity ranged from 10% to 80%, with only four samples showing p53 expression positivity of more than 30%. In silico p53 activity was found to have no independent prognostic value. Conclusions: p53negative tissue may be optimally subjected to TP53 sequencing. TP53 termination mutations may represent a subgroup of patients with significantly shorter survival and may therefore be considered for individualized follow-up programs.

Ovarian cancer (OC); p53; TP53; Overall survival (OS), neoplasm proteins

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