Patients With Bladder Cancer
Loss of intercellular adhesion facilitates tumor invasion. To clarify the relation between altered expression of cell adhesion molecules and progression of T1 superficial bladder tumors, 101 cases (71 T1 tumors, 30 T2/T3 tumors) were examined immunohistochemically for E-cadherin and α-, β-, and γ-catenins. A highly significant correlation was observed between the decreased expression of all molecules and increased TNM stage (P < .001). Univariate analysis, performed in cases of T1 tumors, revealed association of abnormal E-cadherin with β-catenin diminution. Survival curves were established with the Kaplan-Meier method and analyzed according to clinical and histopathologic parameters using the log-rank test. Cox multivariate analysis revealed only γ-catenin as an independent predictor of progression-free survival in patients with stage T1 bladder urothelial tumors. The characterization of T1 tumors that will progress could lead to the identification of patients who might benefit from surgery to avoid vesical muscle invasion and, consequently, metastasis.
Urothelial carcinoma is the most common solid malignancy of the bladder. It is distinguished as muscle-invasive carcinoma or superficial bladder tumor. Muscle-invasive carcinomas generally are associated with poor prognosis, whereas the clinical outcome of superficial bladder tumors is relatively unpredictable. The recurrence rate of T1 superficial bladder tumors is high (80%), and 40% of them will progress to a poorer prognosis muscle-invasive disease. Stage and grade, based on histopathologic criteria, are classic prognostic variables that permit evaluating recurrence or progression of the disease, which is useful for clinical purposes. The identification of new prognostic markers allowing improvement of the biologic assessment of the T1 superficial tumors could be of great clinical value for disease management.
Tumor progression is accompanied by altered expression of cell adhesion molecules such as cadherins. E-cadherin, one subtype of transmembrane glycoprotein that mediates calcium-dependent adhesion of cells, is expressed specifically in epithelia and is involved in maintenance of their phenotype. Its cytoplasmic domain associates with cytoplasmic proteins termed catenins. β-Catenin or γ-catenin binds directly, whereas α-catenin links the bound β-catenin or γ-catenin to the actin microfilament network of the cellular cytoskeleton. This binding is essential for stable cell-to-cell adhesion. Reduction in expression of these molecules has been reported in human cancers.
In the bladder, studies have shown that decreased E-cadherin expression was linked to a loss of differentiation and tumor aggressiveness, and loss of E-cadherin expression was correlated with high grade and advanced stage. Few studies have compared the predictive value of this adhesion molecule with that of clinical and pathologic parameters. E-cadherin status seems to be an independent predictor of disease progression in patients treated with cystectomy for urothelial carcinomas. When urothelial carcinomas become invasive, E-cadherin expression decreases in direct proportion to the depth of invasion. Results on the independent clinical value of E-cadherin immunostaining are controversial. Reduced expression of E-cadherin also was observed in the poorly differentiated and invasive tumor–derived cells. Few data are available on altered α-, β-, and γ-catenin expression and tumorigenesis in the bladder. Abnormal expression of these cadherin cytoplasmic partners correlated significantly with tumor grade, advanced stage, and poor survival.
The present study was undertaken to examine a large series of 101 urothelial carcinomas from stage T1 to T2/T3 for the expression of the adhesion molecules E-cadherin and α-, β-, and γ-catenin. The objectives of this study were as follows: (1) establish the relationship between expression of these adhesion molecules and the clinical and pathologic parameters, (2) define within T1 tumors their value in distinguishing T1a (minimally invasive) from T1b (invasive) tumors, (3) evaluate their use as predictive factors in the progression of T1a and T1b tumors, and (4) assess their potential prognostic role within T1 superficial bladder tumors in predicting survival without progression. Early detection within T1 tumors of a subgroup that will progress might successfully identify potentially lethal lesions (T1b?) before they become muscle invasive, and this could help identify patients who might benefit from surgery to avoid vesical muscle invasion and, consequently, metastasis.
Loss of intercellular adhesion facilitates tumor invasion. To clarify the relation between altered expression of cell adhesion molecules and progression of T1 superficial bladder tumors, 101 cases (71 T1 tumors, 30 T2/T3 tumors) were examined immunohistochemically for E-cadherin and α-, β-, and γ-catenins. A highly significant correlation was observed between the decreased expression of all molecules and increased TNM stage (P < .001). Univariate analysis, performed in cases of T1 tumors, revealed association of abnormal E-cadherin with β-catenin diminution. Survival curves were established with the Kaplan-Meier method and analyzed according to clinical and histopathologic parameters using the log-rank test. Cox multivariate analysis revealed only γ-catenin as an independent predictor of progression-free survival in patients with stage T1 bladder urothelial tumors. The characterization of T1 tumors that will progress could lead to the identification of patients who might benefit from surgery to avoid vesical muscle invasion and, consequently, metastasis.
Urothelial carcinoma is the most common solid malignancy of the bladder. It is distinguished as muscle-invasive carcinoma or superficial bladder tumor. Muscle-invasive carcinomas generally are associated with poor prognosis, whereas the clinical outcome of superficial bladder tumors is relatively unpredictable. The recurrence rate of T1 superficial bladder tumors is high (80%), and 40% of them will progress to a poorer prognosis muscle-invasive disease. Stage and grade, based on histopathologic criteria, are classic prognostic variables that permit evaluating recurrence or progression of the disease, which is useful for clinical purposes. The identification of new prognostic markers allowing improvement of the biologic assessment of the T1 superficial tumors could be of great clinical value for disease management.
Tumor progression is accompanied by altered expression of cell adhesion molecules such as cadherins. E-cadherin, one subtype of transmembrane glycoprotein that mediates calcium-dependent adhesion of cells, is expressed specifically in epithelia and is involved in maintenance of their phenotype. Its cytoplasmic domain associates with cytoplasmic proteins termed catenins. β-Catenin or γ-catenin binds directly, whereas α-catenin links the bound β-catenin or γ-catenin to the actin microfilament network of the cellular cytoskeleton. This binding is essential for stable cell-to-cell adhesion. Reduction in expression of these molecules has been reported in human cancers.
In the bladder, studies have shown that decreased E-cadherin expression was linked to a loss of differentiation and tumor aggressiveness, and loss of E-cadherin expression was correlated with high grade and advanced stage. Few studies have compared the predictive value of this adhesion molecule with that of clinical and pathologic parameters. E-cadherin status seems to be an independent predictor of disease progression in patients treated with cystectomy for urothelial carcinomas. When urothelial carcinomas become invasive, E-cadherin expression decreases in direct proportion to the depth of invasion. Results on the independent clinical value of E-cadherin immunostaining are controversial. Reduced expression of E-cadherin also was observed in the poorly differentiated and invasive tumor–derived cells. Few data are available on altered α-, β-, and γ-catenin expression and tumorigenesis in the bladder. Abnormal expression of these cadherin cytoplasmic partners correlated significantly with tumor grade, advanced stage, and poor survival.
The present study was undertaken to examine a large series of 101 urothelial carcinomas from stage T1 to T2/T3 for the expression of the adhesion molecules E-cadherin and α-, β-, and γ-catenin. The objectives of this study were as follows: (1) establish the relationship between expression of these adhesion molecules and the clinical and pathologic parameters, (2) define within T1 tumors their value in distinguishing T1a (minimally invasive) from T1b (invasive) tumors, (3) evaluate their use as predictive factors in the progression of T1a and T1b tumors, and (4) assess their potential prognostic role within T1 superficial bladder tumors in predicting survival without progression. Early detection within T1 tumors of a subgroup that will progress might successfully identify potentially lethal lesions (T1b?) before they become muscle invasive, and this could help identify patients who might benefit from surgery to avoid vesical muscle invasion and, consequently, metastasis.
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