The clinicopathological significance and prognostic value of β-catenin Ser45-phosphorylation expression in esophageal squamous cell carcinoma

Int J Clin Exp Pathol. 2019 Sep 1;12(9):3507-3513. eCollection 2019.

Abstract

β-Catenin is a multifunctional protein which plays a central role in physiological homeostasis, and it acts both as an adaptor protein for intracellular adhesion and a transcriptional co-regulator. As a pivotal component of the Wnt signaling pathway, the accumulation of β-catenin in the cytoplasm/nucleus leads to many diseases including cancer. The phosphorylation at Ser45 of β-catenin causes the degradation of β-catenin, which makes β-catenin at a very low level. It has been shown that phosphorylation at Ser45 of β-catenin is closely related to the occurrence and development of tumors. However, little is known about the exact role of β-catenin Ser45-phosphorylation in esophageal squamous cell carcinoma (ESCC).

Purpose: The present study was aimed at exploring the role and the prognostic value of the expression of β-catenin Ser45-phosphorylation in ESCC.

Methods: The expression of phosphorylation at Ser45of β-catenin was detected by immunohistochemistry in 90 cases of ESCC and their corresponding adjacent nonneoplastic esophageal tissues (n = 90). We then evaluated the relationships among the expressions of phosphorylation at Ser45 of β-catenin, the clinicopathological parameters, and the prognoses of the ESCC patients.

Results: The expression level of phosphorylation at Ser45 of β-catenin in ESCC was 65.6% (59/90), significantly lower than the expression level in nonneoplastic esophageal tissues, where it was 88.9% (80/90), (X2 = 10.340, P = 0.003). The expression of β-catenin Ser45-phosphorylation was significantly related to the degree of tumor cell differentiation, but not to age, gender, tumor size, AJCC clinical stage, or lymphatic metastasis. In univariate and multivariate Cox regression analyses, we found that lymphatic invasion and depth of invasion were independent risk factors for the poor prognosis of ESCC patients. Furthermore, a survival analysis revealed that the positive expression of β-catenin Ser45-phosphorylation had a significantly better survival date than the negative group after curative surgery.

Conclusion: β-catenin Ser45-phosphorylation may play an important role in the pathogenesis and development of ESCC and may provide clinically useful prognostic information.

Keywords: esophageal squamous cell carcinoma (ESCC); immunohistochemistry (IHC); phosphorylation at Ser45 of β-catenin; prognosis; β-catenin.