Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

Abstract

ARTIcLE INFO _________________________________________________________ ___________________Introduction: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and α-, β-and γ-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. Materials and Methods: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. Results: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). Conclusions: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of α-catenin expression is related to tumor size in upper tract urothelial carcinomas.

A randomized phase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma

“…Most studies have associated tissue E-cadherin expression loss with UC recurrence/progression. [47][48][49][50][51][52][53][54][55][56][57][58][59][60] A higher plasma sE-cad level has been associated with bladder cancer in comparison with healthy controls; a higher preoperative plasma sEcad level has been associated with nodal metastases and shorter PFS in patients treated with radical cystectomy. 61 Our findings are exploratory, and the role of sE-cad in UC merits further investigation.…”

Transcription Regulation of E-Cadherin by Zinc Finger E-Box Binding Homeobox Proteins in Solid Tumors

“…In plasmacytoid urothelial carcinoma, complete loss of E-cadherin in the cell membrane is found in more than 70% and nuclear accumulation is detected in 48% of the patients [43]. In urothelial carcinoma, E-cadherin level is an indicator of poor prognosis with linking to tumor recurrence and disease-free survival rates [44]. Methylation analysis showing that promoter DNA hypermethylation is a major contributor, which attenuates transcription activity of the E-cadherin gene.…”

Identification of Significant Prognostic Tissue Markers Associated with Survival in Upper Urinary Tract Urothelial Carcinoma Patients Treated with Radical Nephroureterectomy: A Retrospective Immunohistochemical Analysis Using Tissue Microarray

“…Tissue microarray (TMA) of surgical specimens, and the expression of immunohistochemical tissue markers, may provide important clues to better understand the pathogenetic characteristics of UTUC and identify universal prognostic markers, which will aid in estimating more precise prognoses of UTUC after surgery. Therefore, in this study, 27 potential urothelial carcinoma-related tissue markers from previous urothelial carcinoma-related tissue studies and National Cancer Center bladder cancer panel [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] were applied immunohistochemically (IHC) to the TMA of specimens from patients with UTUC who underwent RNU, in order to identify any significant prognostic tissue markers of survival, including intravesical recurrence-free survival (IVRFS), disease-free survival (DFS), and overall survival (OS).…”