A small cohort study found that p53 null mutations confer a particularly severe prognosis in high-grade serous ovarian cancers.
Epithelial ovarian cancer is the fifth most common cause of female cancer-related mortality in the developed world. The most frequent type of epithelial ovarian cancer is high-grade serous ovarian cancer (HGSOC).
A cohort study published in Frontiers in Immunology assessed the implications of p-53 null mutations in HGSOC prognosis and the diagnostic capability of immunohistochemistry in discriminating between null and missense TP53 mutations.
Patient Characteristics
A total of 34 patients with HGSOCs were enrolled (n=16 in the p53 null group, n=18 in the p53 overexpressed group). The mean age at diagnosis was 68.8 years in the p53 null group and 64.1 years in the p53 overexpressed group (the difference was statistically significant). The median follow-up duration was 15 months.
TP53 Null Mutations Significantly Increase Tumor-Related Death Risk
A significant association was observed between p53 null and increased risk of HGSOC-related death (hazard ratio (HR): 3.64) compared with p53 overexpressed. An even more significant association was observed between p53 null and increased risk of HGSOC-related death within 24 months of follow-up (HR: 6.09) compared to p53 overexpressed. Conversely, the difference in progression-free survival was not statistically significant between the groups.
Immunohistochemical Staining for p53 Divides HGSOC Patients Into Two Groups
All 34 HGSOCs (100%) demonstrated aberrant p53 immunohistochemical expression. Meanwhile, the two study controls, low-grade serous tumor and mucinous carcinoma, had wild-type TP53, with p53 expression of 20% and 5%, respectively.
Of the 18 p53 overexpressed samples, 16 (88.9%) had a missense mutation, all occurring in the p53 DNA-binding domain (DBD); regarding the remaining two, no mutation was identified in exons 2–11 of the TP53 gene in one, while the other could not be evaluated due to poor DNA quality. The p53 null pattern on immuno-labeling was always associated with mutations. None of the nonsense mutation samples exhibited p53 staining.
Concordance Between TP53 Mutations and Immunohistochemistry
Of the 34 HGSOCs analyzed for TP53 mutation by Sanger sequencing, 32 (94.1%) had mutations of biological and clinical interest. Combining the immunohistochemical staining patterns of p53 null and p53 overexpression, the immunohistochemical analysis correlated with the mutational analysis in 94.1% of cases.
Most of the TP53 mutations with the p53 null immunophenotype (81.25%, 13/16) were located in the p53 DBD. ‘Hot-spot’ codons for mutation residing within the p53 DBD included p.Arg175 and p.Gly245Ser. Most of the mutations identified through Sanger sequencing were pathogenic or likely pathogenic on analysis.
Source:
Biatta, C. M., Paudice, M., Greppi, M., Parrella, V., Parodi, A., De Luca, G., Cerruti, G., Mammoliti, S., Caroti, C., Menichini, P., Fronza, G., Pesce, S., Marcenaro, E., & Vellone, V. G. (2023). The fading guardian: clinical relevance of TP53 null mutation in high-grade serous ovarian cancers. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1221605
