Expression of YES-associated protein (YAP) and its clinical significance in breast cancer tissues

Hum Pathol. 2017 Oct:68:166-174. doi: 10.1016/j.humpath.2017.08.032. Epub 2017 Sep 9.

Abstract

The transcriptional co-activator YES-associated protein (YAP) has been reported to act as both an oncogene and tumor suppressor in breast cancers. In this study, we evaluated YAP expression immunohistochemically in 324 breast cancer tissues and correlated the expression with clinicopathological findings and patient survival data. Additionally, we reviewed the literature to clarify the role of YAP in breast cancer. We detected YAP, estrogen receptor, progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) expression and a Ki67 labeling index >20% in 53.4%, 49.0%, 45.0%, 28.3%, and 57.4% of invasive ductal carcinoma tissues, respectively. YAP is mainly localized within the tumor cell nuclei, and its expression was associated with the PR status and luminal A subtype. YAP expression also inversely correlated with the HER2 and Ki67 levels and lymph node metastasis. Kaplan-Meier curves revealed associations of YAP expression with favorable disease-free survival (DFS) and overall survival in patients with luminal A breast cancer and with favorable DFS association among patients with invasive ductal carcinoma, luminal B (HER2-), and luminal B (HER2+) breast cancers. A multivariate Cox analysis revealed that YAP expression and PR status were independent favorable predictors of DFS and overall survival, respectively, among patients with breast cancer, whereas tumor-node-metastasis stage and an old age were independent predictors of a poor DFS. Our results, together with the literature review findings, suggest that YAP could be a prognostic marker in patients with breast cancer.

Keywords: Breast cancer; Disease-free survival; Immunohistochemistry; Overall survival; Yap.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis*
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma / chemistry*
  • Carcinoma / mortality
  • Carcinoma / secondary
  • Carcinoma / therapy
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis
  • Lymphatic Metastasis
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Phosphoproteins / analysis*
  • Proportional Hazards Models
  • Receptor, ErbB-2 / analysis
  • Receptors, Progesterone / analysis
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Transcription Factors
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Phosphoproteins
  • Receptors, Progesterone
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2