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

<b>Background</b>: 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 <i>TP53</i> mutation, remains largely unknown. <b>Methods</b>: 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). <b>Results</b>: 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 <i>p</i> values ≤ 0.01), and poor breast cancer specific survival (BCSS) (<i>p</i> = 0.013). In <i>TP53</i> mutant breast cancers, high p73 was significantly associated with aggressive histopathological features (all <i>p</i> ≤ 0.001) and poor BCSS (<i>p</i> = 0.001) but not in p53 wild-type tumours. <b>Conclusions</b>: 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.