Introduction/Background The role of TP53 in tumor initiation and progression is widely studied. Depending on the histological subtype there are mutation rates in ovarian cancer (OC) of up to 95%. Most available studies assess the presence or absence of a TP53 mutation without taking into consideration the specific localisation and function of the mutation. The influence of exon specific TP53 mutations on the tumor biology was examined.
Methodology DNA samples from a total of 189 OC patients that had been diagnosed between the years of 1989 and 2014 were analysed using next-generation sequencing and the TruSight Cancer panel. Correlations between the presence of TP53 mutation and clinicopathological features were analysed using Chi-quadrat test. Survival analysis were performed with Kaplan-Meier and Cox regression.
Results Patients in the TP53 wild-type group demonstrated a statistically significant longer progression free survival (PFS) (p=0.003) and overall survival (OS) (p=<0.001) than those in the TP53-mutant group. In HGSOC a statistically significant difference in PFS of patients with tumors harbouring TP53 mutations in exons 1–5 compared with exons 6–8 (Median: 2.95 vs. 1.31 years) was revealed. A similar effect has been shown for the OS (Median: 3.62 vs. 3.01 years). However, cancers with TP53 mutations in exons 9–11 exhibited no difference in the PFS (p=0.87) and OS (p=0.78) when compared with TP53 wild-type cancers. Tumors with TP53 mutations with a risk of pathogenicity of >95% had a risk for progression (RR: 1.78; p=0.025), which was significantly higher in comparison to the wild-type cancers.
Conclusion This study revealed that different TP53 mutations have different effects on the biology of OC. Therefore accurate assessment of the locus-specific TP53 status in OCs is essential to understand their malignant phenotype and differences in chemotherapy responsiveness with the possibility to predict their clinical course.
Disclosure Nothing to disclose.
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