Reduced expression of catenin subtypes is a potential indicator of unfavorable prognosis in esophageal squamous cell carcinoma

Abstract

Abstract. Catenins are cytoplasmic proteins that play a pivotal role in cell adhesion. Conflicting results regarding the significance of their expression in esophageal squamous cell carcinoma (ESCC) have been reported. The expression of ·-, ß-and Á-catenin was examined using immunohistochemical methods in 69 samples collected from patients with ESCC who were surgically treated without any preoperative induction therapy. Reduced ·-, ß-and Á-catenin expression was observed in 48 (69.7%), 36 (52.2%) and 44 (63.8%) ESCC samples, respectively. According to univariate analysis, ESCC patients exhibiting the reduced expression of ß-catenin (P=0.028), Á-catenin (P=0.010), ·-and Á-catenin combined (P=0.047) or ß-and Á-catenin combined (P=0.046) had a significantly more unfavorable rate of survival. Multivariate analysis demonstrated that the reduced expression of Á-catenin (P=0.015) as well as lymph node metastasis (P=0.015) could serve as independent prognostic indicators of unfavorable prognosis in ESCC patients. Reduced immunohistochemical expression of Á-catenin may thus prove to be a powerfull and useful predictor of prognosis in patients with ESCC. IntroductionThe migration of cancer cells from the cancer nest is an initial event in the formation of tumor metastasis (1). Previous investigations have demonstrated that the expression of adhesion molecules, which prevent cancer cells from detaching, is a potential indicator of favorable prognosis in patients and/or of less invasive behavior in gastrointestinal cancer types, including esophageal squamous cell carcinoma (ESCC) (2-4).Among the various adhesion molecules, the expression of E-cadherin has primarily been investigated, and a significant correlation between its expression and a favorable prognosis in cancer patients, including those with ESCC, has been reported (5-7).Catenins (·-, ß-and Á-) are cytoplasmic proteins that bind to the conserved tail of the epithelial E-cadherin molecule and play a crucial role in E-cadherin-mediated intracellular signal transduction and cell adhesion. The cytoplasmic domain of E-cadherin binds to ß-or Á-catenin, while ·-catenin binds to the E-cadherin -ß-and -Á-catenin complexes to maintain the cellular cytoskeleton (8).While the immunohistochemical expression of ·-, ß-and Á-catenin in ESCC has been examined, the results reported regarding their clinicopathological significance for patient prognosis have been inconsistent (5,6,9-13). The present study used surgically dissected samples of ESCC to investigate the immunohistochemical expression of ·-, ß-and Á-catenin in order to determine their combined effect on the prognosis of patients with ESCC. Patients and methodsPatients and samples. Sixty-nine consecutive specimens of ESCC from patients surgically treated in our department between 1992 and 2003 were obtained. The study population consisted of 63 men and 6 women with a median age of 64 years (range 42-83). Preoperative induction therapy was not performed in any of the cases. Continuous follow-up of the patients was carried ou...

Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ

“…However, plakoglobin may function as a tumor/metastasis suppressor independent of its adhesive function by modulating Rho, Fibronectin and vitronectin-dependent Src signaling (Todorović et al, 2010;Franzen et al, 2012), by acting as a transcriptional repressor of oncogenic Myc (Williamson et al, 2006) and by increasing the expression of metastasis suppressors such as Nm23 (Aktary et al, 2010) and 14-3-3s. These in vitro observations are supported by clinical studies that have shown decreased plakoglobin expression leads to tumorigenesis, increased risk of metastasis and poor overall prognosis in various tumors (Pantel et al, 1998;Kanazawa et al, 2008;Närkiö-Mäkelä et al, 2009;Nozoe et al, 2009;Aktary and Pasdar, 2012;Holen et al, 2012).…”

Prognostic Significance of Beta-Catenin Expression in Patients with Esophageal Carcinoma: a Meta-analysis

“…Li et al, 2009;Nozoe et al, 2009;Situ et al, 2010;Chen et al, 2011;Wang et al, 2011;Lv et al, 2012) investigating the correlation between β-catenin expression and the OS of EC patients were included in the metaanalysis, of which nine studies (Shiozaki et al, 2000;Hsu et al, 2008;Lin et al, 2008;Li et al, 2009;Nozoe et al, 2009;Situ et al, 2010;Chen et al, 2011;Wang et al, 2011;Lv et al, 2012) investigated Asian patients, and one (Krishnadath et al, 1997) investigated European patients. The studies were conducted between 1997 and 2012, and the number of patients they investigated ranged from 40 to 227.…”

“…The studies were conducted between 1997 and 2012, and the number of patients they investigated ranged from 40 to 227. Nine studies (Shiozaki et al, 2000;Hsu et al, 2008;Lin et al, 2008;Li et al, 2009;Nozoe et al, 2009;Situ et al, 2010;Chen et al, 2011;Wang et al, 2011;Lv et al, 2012) investigated patients with ESCC, and one (Krishnadath et al, 1997) investigated EAC. Although all the studies used immunohistochemical analysis to examine the expression of β-catenin, they made different criteria of β-catenin aberrant expression.…”

“…Although all the studies used immunohistochemical analysis to examine the expression of β-catenin, they made different criteria of β-catenin aberrant expression. HRs with 95% CIs were reported directly in three studies (Hsu et al, 2008;Situ et al, 2010;Lv et al, 2012), calculated from available data in six studies (Krishnadath et al, 1997;Shiozaki et al, 2000;Lin et al, 2008;Li et al, 2009;Nozoe et al, 2009;Wang et al, 2011), and extrapolated from Kaplan-Meier curves in one study (Chen et al, 2011). As for the statistical methods used to calculate HRs, four studies used multivariate analysis (Shiozaki et al, 2000;Hsu et al, 2008;Situ et al, 2010;Lv et al, 2012), and the others used univariate analysis.…”

“…It has been reported that aberrant expression of β-catenin was associated with the poor prognosis of non-small cell lung cancer (NSCLC) (Mei et al, 2013), and colorectal cancer (CRC) (Chen et al, 2013). Many studies also reported that β-catenin was involved in the development of EC, however, its prognostic significance for EC patients remains controversial (Krishnadath et al, 1997;Shiozaki et al, 2000;Hsu et al, 2008;Lin et al, 2008;Li et al, 2009;Nozoe et al, 2009;Situ et al, 2010;Chen et al, 2011;Wang et al, 2011;Lv et al, 2012). Therefore, we conducted this meta-analysis to determine whether β-catenin could be a prognosis factor in EC.…”