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. 2023 Aug 23:14:1221605.
doi: 10.3389/fimmu.2023.1221605. eCollection 2023.

The fading guardian: clinical relevance of TP53 null mutation in high-grade serous ovarian cancers

Chiara M Biatta  1 , Michele Paudice  1   2 , Marco Greppi  3 , Veronica Parrella  1 , Alessia Parodi  1 , Giuseppa De Luca  4 , Gianna Maria Cerruti  4 , Serafina Mammoliti  5 , Cinzia Caroti  6 , Paola Menichini  7 , Gilberto Fronza  7 , Silvia Pesce  3 , Emanuela Marcenaro  3   8 , Valerio G Vellone  1   9
Affiliations

The fading guardian: clinical relevance of TP53 null mutation in high-grade serous ovarian cancers

Chiara M Biatta et al. Front Immunol. .

Abstract

Background: we evaluated the concordance between immunohistochemical p53 staining and TP53 mutations in a series of HGSOC. Moreover, we searched for prognostic differences between p53 overexpression and null expression groups.

Methods: patients affected by HGSOC were included. For each case p53 immunohistochemical staining and molecular assay (Sanger sequencing) were performed. Kaplan-Meier survival analyses were undertaken to determine whether the type of TP53 mutation, or p53 staining pattern influenced overall survival (OS) and progression free survival (PFS).

Results: 34 HGSOC were considered. All cases with a null immunohistochemical p53 expression (n=16) showed TP53 mutations (n=9 nonsense, n=4 in-frame deletion, n=2 splice, n=1 in-frame insertion). 16 out of 18 cases with p53 overexpression showed TP53 missense mutation. Follow up data were available for 33 out of 34 cases (median follow up time 15 month). We observed a significant reduction of OS in p53 null group [HR = 3.64, 95% CI 1.01-13.16].

Conclusion: immunohistochemical assay is a reliable surrogate for TP53 mutations in most cases. Despite the small cohort and the limited median follow up, we can infer that HGSOC harboring p53 null mutations are a more aggressive subgroup.

Keywords: TP53; high grade serous ovarian carcinoma; immunohistochemistry; ovarian cancer; sanger sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Comparison of immunohistochemistry expression of biomarkers routinely used in HGSOC diagnosis. ER, Estrogen Receptor; PR, Progesteron receptor. **p value>0.01.
Figure 2
Figure 2
(A) Kaplan-Meier survival curve analyses in HGSOCs. Kaplan-Meier survival curve analysis of TP53 mutation-positive HGSOCs for Death Of the Disease (DOD), in months, of patients with p53 overexpression compared to patients with p53 null. (B) Kaplan-Meier survival curve analyses in HGSOCs (24 months). Kaplan-Meier survival curve analysis of TP53 mutation-positive HGSOCs for DOD.
Figure 3
Figure 3
(A) Percentage of the different types of TP53 in p53 null (N=16) and p53 overexpressed (N=18). (B) Percentage of mutations in each exon of TP53 in p53 null and p53 overexpressed.
See this image and copyright information in PMC

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