# Clinicopathological Significance of Transcription Factor p73 in Breast Cancers: Protein Expression and Transcriptomic Study

## TL;DR

This study explores how the p73 protein relates to aggressive breast cancer traits and poor prognosis, especially in tumors with p53 mutations.

## Contribution

The study identifies cytoplasmic p73 as a potential marker for aggressive breast cancer and poor prognosis in TP53-mutant tumors.

## Key findings

- High cytoplasmic p73 is linked to aggressive tumor features and poor survival in breast cancer patients.
- The association is strongest in TP53-mutant tumors, with significant correlations to histopathological markers and survival outcomes.
- p73 may play a role in breast cancer progression when p53 is mutated.

## Abstract

Background: p73, a member of the p53 family of transcription factors, plays important roles in DNA repair, cell proliferation, angiogenesis, invasion, metastasis, immune evasion, and cytotoxic therapy response. The clinicopathological significance of p73 in breast cancer, particularly in the context of TP53 mutation, remains largely unknown. Methods: Clinicopathological significance of p73 and p53 protein expression was evaluated in 1369 invasive BC and 317 ductal carcinomas in situ (DCIS), including in p53 wild-type or p53 mutant tumours. p73 transcripts and splice variants were investigated in breast cancer genomes (TCGA). Results: High cytoplasmic p73 was significantly associated with high tumour grades, high pleomorphism scores, high mitotic scores, high risk Nottingham prognostic index, negative expression of oestrogen receptors (ERs), triple negative phenotypes (all p values ≤ 0.01), and poor breast cancer specific survival (BCSS) (p = 0.013). In TP53 mutant breast cancers, high p73 was significantly associated with aggressive histopathological features (all p ≤ 0.001) and poor BCSS (p = 0.001) but not in p53 wild-type tumours. Conclusions: Cytoplasmic p73 may be a marker of aggressive phenotype and worse prognosis, particularly in p53 mutant breast cancer. p73, in conjunction with altered p53 expression, may be involved in breast cancer pathogenesis.