title: Prognostic impact of TAZ and β-catenin expression in adenocarcinoma of the esophagogastric junction.
abstract: BACKGROUND
  TAZ is a downstream agent of Hippo signal pathway. β-catenin is a cell adhesion molecule associated with the invasion and metastasis of carcinomas as well as a critical component of Wnt pathway. TAZ and β-catenin have long been thought to play a vital role in tumour development and progression. This study aimed to detect expression of TAZ and β-catenin in adenocarcinoma of the esophagogastric junction (AEG) and explore their clinicopathological significance.
  
  
  METHODS
  The expression of TAZ and β-catenin were detected by immunohistochemistry of 135 AEG samples, and analyzed with complete clinicopathological features. Overall survival rates were also calculated using the Kaplan-Meier method. Cox proportional hazard model was performed to assess the prognostic values. 37 normal mucosa and 41 dysplasia samples of esophagogastric junction (EGJ) were studied comparably.
  
  
  RESULTS
  TAZ protein showed a strictly nuclear staining pattern in AEG and dysplasia with IHC. Expression of TAZ was higher in dysplasia and AEG compared with normal mucosa (P < 0.001, 0.008). The positive expression rate of nuclear β-catenin was significantly higher in carcinoma and dysplasia than that in normal mucosa (P < 0.001, =0.046). Abnormal expression rate of membranous β-catenin in AEG was significantly higher than that in normal mucosa tissues and dysplasia (P = 0.001, 0.002). In AEG, over expression of TAZ was directly correlated with abnormal nuclear β-catenin expression (r = 0.298, P < 0.001) and membranous β-catenin (r = 0.202, P = 0.019). Patients with abnormal TAZ or β-catenin expression of AEG exhibited a shorter overall survival (OS) and lower overall survival rate than those with normal TAZ or β-catenin expression (P < 0.05). In addition, patients with abnormal expression of both TAZ and β-catenin exhibited worst overall survival. In multivariate survival analysis, abnormal expression of TAZ, TAZ & β-catenin (nuclear and membranous) and tumour differentiation were found to be independent prognostic factors related to OS of AEG patients.
  
  
  CONCLUSIONS
  Over expression of TAZ was associated with abnormal expression of β-catenin, which is correlated with poor prognosis of patients with AEG. Abnormal expression of TAZ and TAZ & β-catenin (nuclear and membranous) are independent prognostic factors, so targeting TAZ and β-catenin could prove to be a promising therapeutic strategy for the treatment of AEG.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2558852841276335.
authors.forename: Lidan
authors.initials: L
authors.lastname: Sun
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Wenna
authors.initials: W
authors.lastname: Shi
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Shandong University School of Medicine, 44#,Wenhua Xi Road, Jinan, Shandong 250012, People's Republic of China. jianpingzhang@sdu.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D051176:beta Catenin