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Uroplakin II Gene is Expressed in Transitional Cell Carcinoma but Not in Bilharzial Bladder Squamous Cell Carcinoma: Alternative Pathways of Bladder Epithelial Differentiation and Tumor Formation
PRINCIPLES OF ONCOLOGY AND IMMUNOLOGY, AND TUMORS OF BLADDER, PENIS AND URETHRA
alterations in p53 and Rb were at greater risk for recurrence and for decreasing survival compared to patients whose tumors demonstrated no apparent alteration. Taken together, perturbation of the presumed control function of each of these suppressor genes may permit a cancer to express a more aggressive behavior. The cumulative effect of perturbation of several of these genes may synergize the uncontrolled behavior of a cancer and identify patients in whom more aggressive therapies need to be applied. Michael J. Droller, M.D.
Uroplakin I1 Gene is Expressed in Transitional Cell Carcinoma but Not in Bilharzial Bladder Squamous Cell Carcinoma: Alternative Pathways of Bladder Epithelial Differentiation and Tumor Formation R.-L. WU,I. OSMAN, X.-R. Wu, M.-L. Lu, Z.-F., ZHANG,F.-X. LIANG,R. HAMZA, H. SCHER, C. CORDON-CARDO AND T.-T. SUN,Epithelial Biology Unit, Ronal Perelman Department of Dermatology and Departments of Urology, Microbiology and Pharmacology, Kaplan Cancer Center, New York University Medical School, Memorial Sloan-Kettering Cancer Center, and Veteran Administration Medical Center, New York, New York, and Nutritional Cancer Institute, Cairo, Egypt Cancer Res., 58: 1291-1297,1998 Uroplakins (UPS) are integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. We have cloned the human UP-I1 gene and localized it on chromosome llq23.A survey of 50 transitional cell carcinomas (TCCs) revealed a UP-I1 polymorphism but no tumorspecific mutations. Immunohistochemical staining using rabbit antisera against a synthetic peptide of UP-I1 and against total UPS showed UP reactivity in 39.5% (17of 43 cases) of conventional TCCs, 12.8% (5 of 39)of bilharzial-related TCCs, and 2.7% (1of 36)of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer bilharzial TCCs express UPS than conventional TCCs (12.8versus 40%) raised the possibility that the former are heterogeneous, expressing SCC features to varying degrees. Our data strongly support the hypothesis that urothelium can undergo at least three pathways of differentiation: (a) urothelium-type pathway; (b) epidermis-type pathway; and (c) glandular-type pathway, characterized by the production of UPS, Kl/K10 keratins, and secreted glycoproteins, respectively. Vitamin A deficiency and mesenchymal factors may play a role in determining the relative contributions of these pathways to urothelial differentiation as well as to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof.
Editorial Comment: Uroplakins are a component of the urothelial plasma membrane that bind to the cytoskeleton and presumably stabilize the urothelial luminal surface during bladder distention. Previous studies have demonstrated uroplakins in nearly all noninvasive bladder cancers, in more than half of invasive bladder cancers and in two-thirds of urothelial metastases. They have not been observed in nonurothelial malignancies, suggesting their possible use as a marker to identify urothelial carcinoma. In demonstrating a down regulation of uroplakin expression in bilharzial related squamous cell carcinoma the authors suggest that the urothelium may proceed along several pathways of differentiation developing into different types of urothelial malignancy. Whether it may be possible to adjust the pathways by which the normal urothelium undergoes malignant transformation to produce a specific cell type of urothelial cancer remains to be investigated. Michael J. Droller, M.D.
Expression of Epidermal Growth Factor Receptor in Urinary Bladder Cancer Metastases
P. BUE,K. WESTER, A. SJOSTROM, A. HOLMBERG, S. NILSSON, J. CARLSSON, J.-E. WESTLIN, C. BUSCHAND P.-U. MALMSTROM, Departments of Urology, Pathology and Oncology, Division of Nuclear Medicine, and Biomedical Radiation Sciences, Uppsala University, Uppsala, Sweden Int. J. Cancer, 76 189-193, 1998 Bladder cancers frequently exhibit an increased number of epidermal growth factor receptors (EGFR) in comparison to normal urothelium. The EGFR could potentially be a target for toxic conjugates. The aim of our study was to compare the expression of EGFR in metastases with concurrent or primary tumour in the urinary bladder using immunohistochemical techniques and a monoclonal antibody. Tumour material from 20 patients was investigated. The majority (13/20)of the metastases were homogeneously stained and showed a moderate to strong membranous staining for EGFR. The expression of EGFR in primary bladder tumours and metastases was similar. There was no indication that tumour tissue exposed t o chemotherapy
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alterations in p53 and Rb were at greater risk for recurrence and for decreasing survival compared to patients whose tumors demonstrated no apparent alteration. Taken together, perturbation of the presumed control function of each of these suppressor genes may permit a cancer to express a more aggressive behavior. The cumulative effect of perturbation of several of these genes may synergize the uncontrolled behavior of a cancer and identify patients in whom more aggressive therapies need to be applied. Michael J. Droller, M.D.
Uroplakin I1 Gene is Expressed in Transitional Cell Carcinoma but Not in Bilharzial Bladder Squamous Cell Carcinoma: Alternative Pathways of Bladder Epithelial Differentiation and Tumor Formation R.-L. WU,I. OSMAN, X.-R. Wu, M.-L. Lu, Z.-F., ZHANG,F.-X. LIANG,R. HAMZA, H. SCHER, C. CORDON-CARDO AND T.-T. SUN,Epithelial Biology Unit, Ronal Perelman Department of Dermatology and Departments of Urology, Microbiology and Pharmacology, Kaplan Cancer Center, New York University Medical School, Memorial Sloan-Kettering Cancer Center, and Veteran Administration Medical Center, New York, New York, and Nutritional Cancer Institute, Cairo, Egypt Cancer Res., 58: 1291-1297,1998 Uroplakins (UPS) are integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. We have cloned the human UP-I1 gene and localized it on chromosome llq23.A survey of 50 transitional cell carcinomas (TCCs) revealed a UP-I1 polymorphism but no tumorspecific mutations. Immunohistochemical staining using rabbit antisera against a synthetic peptide of UP-I1 and against total UPS showed UP reactivity in 39.5% (17of 43 cases) of conventional TCCs, 12.8% (5 of 39)of bilharzial-related TCCs, and 2.7% (1of 36)of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer bilharzial TCCs express UPS than conventional TCCs (12.8versus 40%) raised the possibility that the former are heterogeneous, expressing SCC features to varying degrees. Our data strongly support the hypothesis that urothelium can undergo at least three pathways of differentiation: (a) urothelium-type pathway; (b) epidermis-type pathway; and (c) glandular-type pathway, characterized by the production of UPS, Kl/K10 keratins, and secreted glycoproteins, respectively. Vitamin A deficiency and mesenchymal factors may play a role in determining the relative contributions of these pathways to urothelial differentiation as well as to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof.
Editorial Comment: Uroplakins are a component of the urothelial plasma membrane that bind to the cytoskeleton and presumably stabilize the urothelial luminal surface during bladder distention. Previous studies have demonstrated uroplakins in nearly all noninvasive bladder cancers, in more than half of invasive bladder cancers and in two-thirds of urothelial metastases. They have not been observed in nonurothelial malignancies, suggesting their possible use as a marker to identify urothelial carcinoma. In demonstrating a down regulation of uroplakin expression in bilharzial related squamous cell carcinoma the authors suggest that the urothelium may proceed along several pathways of differentiation developing into different types of urothelial malignancy. Whether it may be possible to adjust the pathways by which the normal urothelium undergoes malignant transformation to produce a specific cell type of urothelial cancer remains to be investigated. Michael J. Droller, M.D.
Expression of Epidermal Growth Factor Receptor in Urinary Bladder Cancer Metastases
P. BUE,K. WESTER, A. SJOSTROM, A. HOLMBERG, S. NILSSON, J. CARLSSON, J.-E. WESTLIN, C. BUSCHAND P.-U. MALMSTROM, Departments of Urology, Pathology and Oncology, Division of Nuclear Medicine, and Biomedical Radiation Sciences, Uppsala University, Uppsala, Sweden Int. J. Cancer, 76 189-193, 1998 Bladder cancers frequently exhibit an increased number of epidermal growth factor receptors (EGFR) in comparison to normal urothelium. The EGFR could potentially be a target for toxic conjugates. The aim of our study was to compare the expression of EGFR in metastases with concurrent or primary tumour in the urinary bladder using immunohistochemical techniques and a monoclonal antibody. Tumour material from 20 patients was investigated. The majority (13/20)of the metastases were homogeneously stained and showed a moderate to strong membranous staining for EGFR. The expression of EGFR in primary bladder tumours and metastases was similar. There was no indication that tumour tissue exposed t o chemotherapy
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