Abstract
BackgroundYes-associated protein 1 (YAP1) is a key effector molecule regulated by the Hippo pathway and described as a poor prognostic factor in breast cancer. Tumor protein 53 (TP53) mutation is well known as a biomarker related to poor survival outcomes. So far clinical characteristics and survival outcome according to YAP1 and TP53 mutation have been poorly identified in breast cancer.Patients and methodsRetrospectively, 533 breast tumor tissues were collected at the Seoul St Mary’s hospital and Gangnam Severance Hospital from 1992 to 2017. Immunohistochemistry with YAP1 and p53 specific antibodies were performed, and the clinical data were analyzed.ResultsMutant p53 pattern was associated with aggressive tumor features and advanced anatomical stage. Inferior overall survival (OS) and recurrence free survival (RFS) were related with mutant p53 pattern cases with low nuclear YAP1 expression (P = 0.0009 and P = 0.0011, respectively). Multivariate analysis showed that mutant p53 pattern was an independent prognostic marker for OS [hazard ratios (HR): 2.938, 95% confidence intervals (CIs): 1.028–8.395, P = 0.044] and RFS (HR: 1.842, 95% CIs: 1.026–3.304). However, in cases with high nuclear YAP1 expression, there were no significantly difference in OS and RFS according to p53 staining pattern.ConclusionWe found that mutant p53 pattern is a poor prognostic biomarker in breast tumor with low nuclear YAP1 expression. Our findings suggest that interaction between nuclear YAP1 and p53 expression pattern impact survival outcomes.
Highlights
Yes-associated protein 1 (YAP1) is a key effector molecule regulated by the Hippo pathway and described as a poor prognostic factor in breast cancer
Multivariate analysis showed that mutant p53 pattern was an independent prognostic marker for overall survival (OS) [hazard ratios (HR): 2.938, 95% confidence intervals (CIs): 1.028–8.395, P = 0.044] and recurrence free survival (RFS) (HR: 1.842, 95% CIs: 1.026–3.304)
YAP1 physically interacts with mutant p53 proteins in breast cancer cells and mutant Tumor protein 53 (TP53) enhanced pro-proliferative transcriptional activity such as cyclin A, cyclin B, and cyclin dependent kinase 1 genes [20]
Summary
Yes-associated protein 1 (YAP1) is a key effector molecule regulated by the Hippo pathway and described as a poor prognostic factor in breast cancer. Tumor protein 53 (TP53) mutation is well known as a biomarker related to poor survival outcomes. Yes-associated protein 1 (YAP1) is a key downstream effector molecule of the Hippo pathway. The p53 protein is functionally inactivated in most of the human malignancies due to both alterations in its regulatory pathways and mutations that directly affect the tumor protein 53 (TP53) gene [12, 13]. Mutations of the TP53 is associated with poor survival outcome in solid cancers including breast cancer [14, 15]. YAP1 physically interacts with mutant p53 proteins in breast cancer cells and mutant TP53 enhanced pro-proliferative transcriptional activity such as cyclin A, cyclin B, and cyclin dependent kinase 1 genes [20]
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