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Yes-associated protein (YAP) is differentially expressed in tumor and stroma according to the molecular subtype of breast cancer.

Authors
 Sang Kyum Kim  ;  Woo Hee Jung  ;  Ja Seung Koo 
Citation
 INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, Vol.7(6) : 3224-3234, 2014 
Journal Title
 INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 
Issue Date
2014
MeSH
Adaptor Proteins, Signal Transducing/analysis ; Adaptor Proteins, Signal Transducing/biosynthesis* ; Biomarkers, Tumor/analysis ; Breast Neoplasms/metabolism ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology* ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kaplan-Meier Estimate ; Ki-67 Antigen/biosynthesis ; Phenotype ; Phosphoproteins/analysis ; Phosphoproteins/biosynthesis* ; Phosphorylation ; Proportional Hazards Models ; Receptor, ErbB-2/biosynthesis ; Receptors, Estrogen/biosynthesis ; Receptors, Progesterone/biosynthesis ; Tissue Array Analysis ; Tumor Microenvironment*
Keywords
Breast cancer ; YAP ; molecular subtype
Abstract
In this study, we aimed to clarify the expression profiles of Yes-associated protein (YAP) and phosphorylated YAP (pYAP) protein and to verify the clinical implication of the expression of YAP protein in human breast cancer. We selected 678 cases of formalin-fixed paraffin-embedded (FFPE) breast cancer tissue to construct tissue microarray (TMA) blocks. We performed immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth receptor-2 (HER-2) and Ki-67 and fluorescent in situ hybridization (FISH) assay for HER-2 on the TMA sections and divided breast cancers into molecular subtypes: luminal A, luminal B, HER-2, triple negative breast cancer (TNBC). Then, we examined YAP and pYAP expression status using immunohistochemical analysis according to the molecular subtypes of breast cancer. We found that HER-2 type breast cancer demonstrated elevated expression level in tumoral cytoplasmic YAP (P = 0.011) and pYAP (P = 0.049). Expressions of stromal YAP (P = 0.002) and pYAP (P < 0.001) were higher in luminal B and HER-2 type breast cancer but lower in TNBC. In univariate analysis, nuclear YAP expression of tumor cells was associated with shorter overall survival (OS) (P = 0.024). Cytoplasmic YAP expression of HER-2 type breast cancer cells negatively affected disease-free survival (DFS) (P = 0.034). In conclusion, we concluded that there was a significant difference in YAP and pYAP expression status according to molecular subtypes and tumoral and cellular components of breast cancers. Finally, we found that nuclear and cytoplasmic YAP expression could be a prognostic marker for breast cancer patients.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Kim, Sang Kyum(김상겸) ORCID logo https://orcid.org/0000-0003-0768-9923
Jung, Woo Hee(정우희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99167
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