title: Yes-associated protein (YAP) is differentially expressed in tumor and stroma according to the molecular subtype of breast cancer.
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.
authors.affiliation: Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
authors.forename: Woo Hee
authors.initials: WH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis / Q000096:biosynthesis*; D010766:Phosphorylation; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D046888:Tissue Array Analysis; D014157:Transcription Factors; D059016:Tumor Microenvironment; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D010750:Phosphoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
keywords: Breast cancer; YAP; molecular subtype