Abstract
Reduced expression of the adhesion molecule E-cadherin has been associated with increased invasiveness and poorer survival in patients with bladder cancer. We have examined soluble E-cadherin (sE-cadherin) and total protein concentrations in urine from patients with bladder cancer (n = 34), non-neoplastic benign urological diseases (n = 14) and healthy controls (n = 21) to determine their diagnostic and prognostic significance. Soluble E-cadherin concentrations of the cancer group were significantly higher (P < 0.001) than those of the controls but the benign group was not significantly different from either the cancer group or the controls. When sE-cadherin concentrations were adjusted for creatinine, similar but more statistically significant results were obtained and the benign group was significantly elevated compared with the controls (P < 0.01). No differences were apparent between the invasive (pT1–4) and non-invasive (pTa) cancers. Urinary total protein concentrations in the cancer group were significantly higher than the controls (P < 0.001) and the benign group (P < 0.05) although no difference was seen between the benign group and patients with non-invasive (pTa) cancer or between the benign group and controls. When expressed as the protein/creatinine index, results were similar but more statistically significant and a significant difference was seen between invasive and non-invasive cancers (P < 0.01). Only the protein/creatinine index correlated significantly with stage of the tumour (P < 0.01). It is concluded that urinary sE-cadherin measurements are of no greater value than urinary total protein.
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16 November 2011
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References
Banks, R. E., Porter, W. H., Whelan, P., Smith, P. H. & Selby, P. J. (1995) Soluble forms of the adhesion molecule E-cadherin in urine. J Clin Path 48: 179–180.
Becker, K. F. & Hofler, H. (1995) Frequent somatic allelic inactivation of the E-cadherin gene in gastric carcinomas. J Natl Cancer Inst 87: 1082–1084.
Bringuier, P. P., Umbas, R., Schaafsma, H. E., Karthaus, H. F. M., Debrugne, F. M. J. & Schalken, J. A. (1993) Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumours. Cancer Res 53: 3241–3245.
Caliskan, M., Turkeri, L. N., Mansuroglu, B., Toktas, G., Aksoy, B., Uncluer, E. & Akdas, A. (1997) Nuclear accumulation of mutant p53 protein: a possible predictor of failure of intravesical therapy in bladder cancer. Br J Urol 79: 373–377.
Cancer Research Campaign Factsheet 9.1 (1997). Cancer Research Campaign, London
Damsky, C. H., Richa, J., Solter, D., Knudsen, K. & Buck, C. A. (1983) Identification and purification of a cell surface glycoprotein mediating intercellular adhesion in embryonic and adult tissue. Cell 34: 455–466.
D’Hallewin, M. A. & Baert, L. (1996) Initial evaluation of the bladder tumour antigen test in superficial bladder cancer. J Urol 155: 475–476.
Dyson, E. H., Will, E. J., Davidson, A. M., O’Malley, A. H., Shepard, H. T. & Jones, R. G. (1992) Use of the urinary protein creatinine index to assess proteinuria in renal transplant patients. Nephrol Dial Transplant 7: 450–452.
Esrig, D., Elmajian, D., Groshen, S., Freeman, J., Stein, J., Chen, S. C., Nichols, P., Skinner, D., Jones, P. & Cote, R. (1994) Accumulation of nuclear p53 and tumour progression in bladder cancer. N Engl J Med 331: 1259–1264.
Gearing, A. J. H. & Newman, W. (1993) Circulating adhesion molecules in disease. Immunol Today 14: 506–512.
Gohji, K., Fujimoto, N., Ohkawa, J., Fujii, A. & Nakajima, M. (1998) Imbalance between serum matrix metalloproteinase-2 and its inhibitor as a predictor of recurrence of urothelial cancer. Br J Cancer 77: 650–655.
Griffiths, T. R. L., Brotherick, I., Bishop, R. I., White, M. D., McKenna, D. M., Horne, C. H. W., Shenton, B. K., Neal, D. E. & Mellon, J. K. (1996) Cell adhesion molecules in bladder cancer: soluble serum E-cadherin correlates with predictors of recurrence. Br J Cancer 74: 579–584.
Hemmingsen, L., Rasmussen, F., Skaarup, P. & Wolf, H. (1981) Urinary protein profiles in patients with urothelial bladder tumours. Br J Urol 53: 324–329.
Hermanek, P. & Sobin, L. H. (eds) (1987). UICC TNM Classification of Malignant Tumours , 4th edn, pp. 65–67. Springer Verlag: Berlin
Hiraguri, S., Godfrey, T., Nakamura, H., Graff, J., Collins, C., Shayesteh, L., Doggett, N., Johnson, K., Wheelock, M., Herman, J., Baylin, S., Pinkel, D. & Gray, J. (1988) Mechanisms of inactivation of E-Cadherin in breast cancer cell lines. Cancer Res 58: 1972–1977.
Hudson, M. A. & Catalona, W. J. (1996). Urothelial tumours of the bladder, upper tracts and prostate. In Adult and Paediatric Urology, Gillenwater JY, Grayhack JT, Howards SS and Duckett JW (eds), pp. 643–694. Mosby: St Louis, MO
Johansson, B. (1975) Urinary protein patterns in patients with uroepithelial tumours. Scand J Urol Nephrol 9: 221–225.
Johansson, B. & Kistner, S. (1975) Proteinuria in patients with uroepithelial tumours with special regard to tumour size, clinical staging and grade of malignancy. Scand J Urol Nephrol 9: 45–49.
Jones, L. W., Levin, A. & Fudenberg, H. H. (1975) Glomerular antigen complexes associated with transitional cell carcinoma. Surg Gynecol Obstet 140: 896–898.
Kanai, Y., Oda, T., Tsuda, H., Ochiai, A. & Hirohashi, S. (1994) Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast. Jpn J Cancer Res 85: 1035–1039.
Kanayama, H., Yokota, K., Kurokawa, Y., Murakami, Y., Nishitani, M. & Kagawa, S. (1998) Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in bladder cancer. Cancer 82: 1359–1366.
Katayama, M., Hirai, S., Kamihagi, K., Nakagawa, K., Yasumoto, M. & Kato, I. (1994a) Soluble E-cadherin fragments increased in circulation of cancer patients. Br J Cancer 69: 580–585.
Katayama, M., Hirai, S., Yasumoto, M., Nishikawa, K., Nagata, S., Otsuka, M., Kamihagi, K. & Kato, I. (1994b) Soluble fragments of E-cadherin cell adhesion molecule increase in urinary excretion of cancer patients, potentially indicating its shedding from epithelial tumour cells. Int J Oncol 5: 1049–1057.
Kinoshita, H., Ogawa, O., Kakehi, Y., Mishina, M., Mitsumori, K., Itoh, N., Yamada, H., Terachi, T. & Yoshida, O. (1997) Detection of telomerase activity in exfoliated cells in urine from patients with bladder cancer. J Natl Cancer Inst 89: 724–730.
Leyh, H., Hall, R., Mazeman, E. & Blumenstein, B. (1997) Comparison of the BARD BTA test with voided urine and bladder wash cytology in the diagnosis and management of cancer of the bladder. Urology 50: 49–53.
Lipponen, P. K. & Eskelinen, M. J. (1995) Reduced expression of E-cadherin is related to invasive disease and frequent recurrence in bladder cancer. J Cancer Res Clin Oncol 121: 303–308.
Mao, L., Schoenberg, M., Scicchitano, M., Erozan, Y., Merlo, A., Schwab, D. & Sidransky, D. (1996) Molecular detection of primary bladder cancer by microsatellite analysis. Science 271: 659–662.
Matsuura, K., Kawanishi, J., Fujii, S., Imamura, M., Hiranos, S., Takeichi, M. & Niitsu, Y. (1992) Altered expression of E-cadherin in gastric cancer tissue and carcinomatous fluid. Br J Cancer 66: 1122–1130.
Mitchell, S., Sheldon, T. & Shaw, A. (1993) Quantification of proteinuria: a re-evaluation of the protein/creatinine ratio for elderly subjects. Age Ageing 22: 443–449.
Mostofi, F. K., Sobin, L. H. & Torloni, H. (1973). Histological typing of urinary bladder tumours. In International Histological Classification of Tumours, 10: World Health Organization: Geneva
O’Brien, P., Gozzo, J., Cronin, W. & Monaco, A. (1980) Qualitative analysis of proteinuria associated with bladder cancer. Invest Urol 17: 28–32.
O’Brien, P., Gozzo, J. J. & Monaco, A. P. (1981) Urinary proteins as biological markers: bladder cancer diagnosis versus urinary tract infection. J Urol 124: 802–803.
Otto, T., Birchmeier, W., Schmidt, U., Hinke, A., Schipper, J., Rubben, H. & Raz, A. (1994) Inverse relation of E-cadherin and autocrine motility factor receptor expression as a prognostic factor in patients with bladder carcinomas. Cancer Res 54: 3120–3123.
Ozawa, M., Engel, J. & Kemler, R. (1990) Single amino acid substitutions in one Ca2+ binding site of uvomorulin abolish adhesive function. Cell 63: 1033–1038.
Parmar, M. K. B., Freedman, L. S., Hargreave, T. B. & Tolley, D. A. (1989) Prognostic factors for recurrence and follow-up policies in the treatment of superficial bladder cancer: report from the British Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party). J Urol 142: 284–288.
Reading, J., Hall, R. R. & Parmar, M. K. B. (1995) The application of a prognostic factor analysis for Ta.T1 bladder cancer in routine urological practice. Br J Urol 75: 604–607.
Rock, R. C., Walker, W. G. & Jennings, C. D. (1986). Nitrogen metabolites and renal function. In Textbook of Clinical Chemistry, Tietz NW (ed), pp. 1254–1316. WB Saunders: Philadelphia
Ross, J. S., Del Rosario, A. D., Figge, H. L., Sheehan, C., Fisher, H. A. G. & Bui, H. X. (1995) E-cadherin expression in papillary transitional cell carcinoma of the urinary bladder. Hum Pathol 26: 940–944.
Sarosdy, M., deVERE White, R., Soloway, M., Sheinfeld, J., Hudson, M., Schellhammer, P., Jarowenko, M., Adams, G. & Blumenstein, B. (1995) Results of a multicentre trial using the BTA test to monitor for and diagnose recurrent bladder cancer. J Urol 154: 379–384.
Shimoyama, Y., Nagafuchi, A., Fujita, S., Gotoh, M., Takeichi, M., Tsukita, S. & Hirohashi, S. (1992) Cadherin dysfunction in a human cancer cell line: possible involvement of loss of α-catenin expression in reduced cell–cell adhesiveness. Cancer Res 52: 5770–5774.
Soloway, M., Briggman, J., Carpinito, G., Chodak, G., Church, P., Lamm, D., Lange, P., Messing, E., Pasciak, R., Reservitz, G., Rukstalis, D., Sarosdy, M., Stadler, W., Thiel, R. & Hayden, C. (1996) Use of a new tumour marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. J Urol 156: 363–367.
Steiner, G., Schoenberg, M. P., Linn, J. F., Mao, L. & Sidransky, D. (1997) Detection of bladder cancer recurrence by microsatellite analysis of urine. Nature Med 3: 621–624.
Syrigos, K., Krausz, T., Waxman, J., Pandha, H., Rowlinson-Busza, G., Verne, J., Epenetos, A. & Pignatelli, M. (1995) E-cadherin expression in bladder cancer using formalin-fixed, paraffin-embedded tissues: correlation with histopathological grade, tumour stage and survival. Int J Cancer 64: 367–370.
Takeichi, M. (1990) Cadherins: a molecular family important in selective cell–cell adhesion. Ann Rev Biochem 59: 237–252.
Takeichi, M. (1993) Cadherins in cancer implications for invasion and metastasis. Curr Opin Cell Biol 5: 806–811.
Tsuji, M., Kojima, Y., Murakami, Y., Kanayama, H. & Kagawa, S. (1997) Prognostic value of Ki-67 antigen and p53 protein in urinary bladder cancer: immunohistochemical analysis of radical cystectomy specimens. Br J Urol 79: 367–372.
Yoshida, K., Sugino, T., Tahara, H., Woodman, A., Bolodeoku, J., Nargund, V., Fellows, G., Goodison, S., Tahara, E. & Tarin, D. (1997) Telomerase activity in bladder carcinoma and its implication for noninvasive diagnosis by detection of exfoliated cancer cells in urine. Cancer 79: 362–369.
Yoshiura, K., Kanai, Y., Ochiai, A., Shimoyama, Y., Sugimura, T. & Hirohashi, S. (1995) Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA 92: 7416–7419.
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Departments of Chemical Pathology, St James’s University Hospital, Leeds, LS9 7TF, UK
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Protheroe, A., Banks, R., Mzimba, M. et al. Urinary concentrations of the soluble adhesion molecule E-cadherin and total protein in patients with bladder cancer. Br J Cancer 80, 273–278 (1999). https://doi.org/10.1038/sj.bjc.6690351
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DOI: https://doi.org/10.1038/sj.bjc.6690351
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