Altered gamma-catenin expression correlates with poor survival in patients with bladder cancer.
OBJECTIVE
We studied the expression of alpha-, beta-, gamma- catenin and E-cadherin in transitional cell carcinoma (TCC) and normal bladder epithelium and correlated these results with pathological and clinical parameters.


METHODS
We used an avidin-biotin immunoperoxidase technique to examine the cellular localization of alpha-catenin, beta-catenin, gamma-catenin and E-cadherin in 68 TCC and 14 normal bladder biopsies.


RESULTS
E-cadherin, alpha-catenin, beta-catenin and gamma-catenin were expressed in a normal membranous pattern in all normal bladder epithelium specimens. Loss of normal surface E-cadherin, alpha-catenin, beta-catenin and gamma-catenin expression was found in 52/68 (76.4%) tumors, 57/68 (83.8%) tumors, 54/68 (79.4%) tumors and 54/68 (79.4%) tumors (p <0.001). There was a significant correlation between the loss of normal membranous expression of catenins and E-cadherin and increased grade (p <0.05). A highly significant correlation was observed between the loss of expression of E-cadherin, alpha-catenin and gamma-catenin, but not beta-catenin, with increased TNM stage (p <0.05). The abnormal expression of gamma-catenin as well as E-cadherin was correlated with poor survival (p <0.05).


CONCLUSIONS
E-cadherin-gamma-catenin complex may be a useful prognostic marker in bladder cancer. Work is in progress to establish whether normal membranous catenin expression can be enhanced by gene transfer or biological therapy to induce a less invasive and metastatic phenotype.
Department of Clinical Oncology, Imperial College of Science Technology and Medicine, Hammersmith Hospital Campus, London, United Kingdom.
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Syrigos
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Harrington
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Waxman
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Krausz
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Pignatelli
D000368:Aged; D015820:Cadherins / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D051180:Desmoplakins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D015996:Survival Rate; D015534:Trans-Activators; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin