Abstract
BackgroundTAZ 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.MethodsThe 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.ResultsTAZ 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.ConclusionsOver 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.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2558852841276335
Highlights
transcriptional coactivator with PDZ-binding motif (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
Expression of TAZ and β-catenin As shown in Figure 1 and Table 1, a positive expression of TAZ was observed in normal mucosa 16.2% (6/37), dysplasia 70.7% (29/41), and adenocarcinoma of the esophagogastric junction (AEG) 40.7% (55/135) and the difference was significant (H = 23.922, P
It is worth reminding that the expression of TAZ in dysplasia is higher than that in AEG (P = 0.001)
Summary
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 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. Adenocarcinoma of the esophagogastric junction (AEG) is defined as carcinoma that crosses the esophagogastric junction (EGJ) line, irrespective of where the tumour epicenter is located, including both distal esophageal and proximal gastric carcinomas [1]. There are still many controversies in its definition, classification, diagnosis and treatment. This study explores the features of AEG to provide some evidence for clinical diagnosis and treatment
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