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. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2558852841276335