Reduced expression of P120 catenin in cholangiocarcinoma correlated with tumor clinicopathologic parameters

Abstract

AIM: To i nve s t i g a t e t h e re l a t i o n s h i p b e t w e e n the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma (ICC). METHODS: An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS: The expression of E-cadherin and P120 was reduced in 27 cases (64.3%) and 31 cases (73.8%), respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade (χ 2 = 9.333, P = 009 and χ 2 = 11.71, P = 0.003), TNM stage (χ 2 = 8.627, P = 0.035 and χ 2 = 13.123, P = 0.004), intrahepatic metastasis (χ 2 = 7.292, P = 0.007 and χ 2 = 4.657, P = 0.041, respectively) and patients' survival (χ 2 = 6.351, P = 0.002 and χ 2 = 4.023, P = 0.000, respectively). In addition, the expression of P120 was in concordance with that of E-cadherin ( χ 2 = 1 3 .7 9 7, P = 0 . 0 0 0 ) , i n d i c a t i n g t h a t t h e expression of P120 may be dependent on that of E-cadherin. Finally, only P120 expression was found to be an independent prognostic factor in Cox regression model (r = 0.088, P = 0.049). CONCLUSION:D o w n-re g u la t e d e x p re s s io n o f E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markers for predicting tumor invasion, metastasis and patients' survival, but only P120 is an independent prognostic factor for ICC.

Periostin promotes malignant potential by induction of epithelial‐mesenchymal transition in intrahepatic cholangiocarcinoma

“…These results suggest that periostin promotes EMT in ICC. The prognostic significance of EMT‐related markers has been increasingly reported in ICC . In addition, a previous in vitro study using ICC cells demonstrated that exogenous periostin stimulation promoted proliferation and invasion through the integrin α5/phosphoinositide 3‐kinase/protein kinase B pathway …”

Genomic and transcriptional alterations of cholangiocarcinoma

“…A number of studies have demonstrated that the representative cell adhesion machinery in epithelia composed of E‐cadherin and beta‐catenin is disrupted in both CCA with and without Ov infection. Immunohistochemical studies have demonstrated that 52–64% of CCA without Ov infection shows reduced expression of E‐cadherin in the analysis of 156 tumors total . Reduced or aberrant expression of beta‐catenin and P‐120 catenin was also reported in 39–97% and 74% of CCA without Ov infection, respectively .…”

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

“…Although, down-regulation of E-cadherin in iCCA has been correlated with poor tumor differentiation, tumor size, advanced pTNM stage, intrahepatic metastasis and lymph node metastasis [25,26,29,31,32,36], its prognostic value is still controversial. Ryu et al, did not find any impact of E-cadherin expression on overall survival (OS) or disease free survival (DFS) [24] whereas other groups demonstrated that E-cadherin loss was significantly associated with these parameters and was an independent prognostic factor [25,32,36]. In eCCA, patients with weak E-cadherin expression displayed lower survival rate than patients with high E-cadherin expression [18] and was also an independent prognostic factor [40].…”

“…While E-cadherin is localized at the plasma membrane in healthy biliary epithelium, its down-regulation and/or ectopic localization, i.e. cytoplasmic internalization, have been reported in malignant cholangiocytes [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Genetic mutations and epigenetic silencing through promoter hypermethylation of the E-cadherin gene (CDH1) are among the mechanisms that account for the down-regulation of E-cadherin [30,33,38].…”