Differential expression of E-cadherin and P-cadherin in pT3 prostate cancer: correlation with clinical and pathological features

Abstract

Cadherins seem to play and important role in prostate cancer (PCa) progression. E-cadherin loss of expression has been associated with poor prognosis; P-cadherin's role is still elusive. Although pT3 PCa is often considered "high-risk cancer," it does not exhibit an uniformly poor prognosis. Herein, we assessed the prognostic value and survival impact of E-cadherin and P-cadherin immunoexpression in pT3 PCa. Radical prostatectomy (RP) specimens from 102 pT3 PCa patients treated between 1991 and 2014 in a single institution were designated for E-cadherin and P-cadherin immunoexpression analysis. A representative block from each specimen was selected for tissue micro-array (TMA) construction, using 3 cores per case. E-cadherin immunoexpression was assessed via a digital image analysis system. For P-cadherin, scoring criteria for HER2 in gastric cancer were used. Clinical records of all patients were reviewed for baseline clinical/pathologic characteristics and follow-up data. E-cadherin-low PCa patients displayed worse disease-specific survival (DSS), although not reaching statistical significance (HR 2.65, 95%CI 0.81-7.88). However, considering the pT3b group only, those with low E-cadherin immunoexpression displayed significantly worse overall-survival (OS) and DSS (HR 3.69, 95%CI 1.18-11.50; HR 5.90, 95%CI 1.40-24.81). No significant differences in survival were found for P-cadherin differential immunoexpression. Furthermore, an association between E-cadherin and P-cadherin immunoexpression (p = 0.019) was found, as among E-cadherin-low PCa, 96.6% were P-cadherin negative. We demonstrated that low E-cadherin immunoexpression discriminates among pT3b PCa patients those with poorer survival and which might benefit from specific therapy. The role of P-cadherin in PCa seems context-dependent deserving further investigation.

Practicability of clinical application of bladder cancer molecular classification and additional value of epithelial-to-mesenchymal transition: prognostic value of vimentin expression

“…In another setting, the EMT signaling pathway and its players have been implicated in acquisition of a more aggressive cancer phenotype among various tumor models, demonstrated both in vitro, in vivo and validated in clinical studies with human specimens [43,44]. The role of expression of epithelial markers such as E-cadherin, the phenomenon of cadherin switch and overexpression of mesenchymal markers (like Snail, Twist, ZEB1/2, Slug and VIM) has been shown across tumor models [45][46][47][48]. BlCa is no exception, with studies evidencing that mesenchymal features significantly associate with higher propensity for disease recurrence, metastatic spread, tumor progression and worse prognosis, including poorer survival and treatment resistance [31,33,[49][50][51][52].…”

Exploring the Relationship between E-Cadherin and β-Catenin Cell Adhesion Proteins and Periacinar Retraction Clefting in Prostatic Adenocarcinoma

“…However, during the progression of prostate cancer, E-cadherin expression can become dysregulated. Reduced levels of E-cadherin are observed in prostatic adenocarcinoma, correlating with increased tumor aggressiveness and metastatic potential [ 15 , 16 , 17 ]. The loss or downregulation of E-cadherin expression in prostate cancer cells diminishes cell–cell adhesion, leading to decreased cohesion between tumor cells.…”

“…E-cadherin and β-catenin proteins are described as valuable tumor markers, as their altered expression has been shown to correlate with increased tumor aggressiveness and dedifferentiation in human cancers, including prostatic adenocarcinoma. A decrease in E-cadherin expression is described to correlate with advanced GSC and advanced pathologic stage in prostatic adenocarcinoma [ 7 , 15 , 16 , 17 , 18 , 19 ]. Lower E-cadherin expression is reported to be related to worse overall-survival and disease-free survival (HR 3.69, 95%CI 1.18–11.50; HR 5.90, 95%CI 1.40–24.81) in the pT3b group of prostatic adenocarcinoma in the study of Ferreira et al [ 15 ].…”

E-Cadherin, Integrin Alpha2 (Cd49b), and Transferrin Receptor-1 (Tfr1) Are Promising Immunohistochemical Markers of Selected Adverse Pathological Features in Patients Treated with Radical Prostatectomy

“…Matrix metalloproteinase to e-cadherin expression ratio exhibited a strong association with non-organ-confined disease and predicted extracapsular extension independently from biopsy Gleason score and PSA [ 31 ]. To date, downregulation of alpha-catenin, which is an intracellular element of e-cadherin, has been suggested as a predictor of unfavorable outcome including baseline grading [ 31 ] and staging [ 31 , 32 , 33 ], positive surgical margins [ 33 ], BCR [ 34 ], as well as cancer-specific survival in organ-confined [ 34 ], locally-advanced [ 35 ], and metastatic [ 32 ] patients. Existing evidence corresponds with our data.…”