The association between the expression of nuclear Yes-associated protein 1 (YAP1) and p53 protein expression profile in breast cancer patients

Abstract

Background 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. So far clinical characteristics and survival outcome according to YAP1 and TP53 mutation have been poorly identified in breast cancer. Patients and methods Retrospectively, 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. Results Mutant 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. Conclusion We 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.

The significance of Hippo pathway protein expression in oral squamous cell carcinoma

“…YAP1 functions as an oncogene; its overexpression inhibits cell contact and promotes cancer cell proliferation and invasion ( 6 ). High expression of YAP1 has frequently been reported in various cancers, such as cervical cancer ( 7 ), head and neck cancer ( 7 ), pancreatic cancer ( 28 ), breast cancer ( 29 ), intrahepatic cholangiocarcinoma ( 30 ), non-small cell lung cancer ( 31 ), and liposarcoma ( 32 ), and is correlated with poor prognosis, while the loss of YAP1 has potential as a clinical marker in small cell lung cancer ( 33 ). Cytoplasmic expression of YAP1 was low in the basal cells of the normal epithelium, dysplastic cells of OED, and cancer cells.…”