High Expression of Human Uroplakin Ia in Urinary Bladder Transitional Cell Carcinoma
Susumu Kageyama
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorCorresponding Author
Tatsuhiro Yoshiki
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
To whom correspondence should be addressed. E-mail: [email protected]Search for more papers by this authorTakahiro Isono
Central Research Laboratory, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorTsutomu Tanaka
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorChoi Jang Kim
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorTakeshi Yuasa
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorYusaku Okada
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorSusumu Kageyama
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorCorresponding Author
Tatsuhiro Yoshiki
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
To whom correspondence should be addressed. E-mail: [email protected]Search for more papers by this authorTakahiro Isono
Central Research Laboratory, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorTsutomu Tanaka
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorChoi Jang Kim
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorTakeshi Yuasa
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorYusaku Okada
Department of Urology, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga 520-2192
Search for more papers by this authorhttp://www.ncc.go.jp/jp/statistics/1999/index_i.html (The last date of access was November 1st 2001.) Cancer Statistics in Japan 1999. The Foundation for Promotion of Cancer Research.
Abstract
Uroplakins (UPs) Ia, Ib, II, and III are tissue-specific and differentiation-dependent transmem-brane proteins of the urothelium. We assessed the usefulness of human UP Ia as a histological marker by examining its expression in urinary bladder transitional cell carcinoma (TCC). A polyclonal antibody against human UP Ia was raised using a synthesized polypeptide. We applied our antibody to various organ tissues, including urothelium, and observed no crossreactivity. Analysis by RT-PCR of normal urothelium, TCC and other organ tissues indicated that the human UP Ia gene expression is highly specialized to urothelium, and is conserved in TCC. Using immunohistochemistry, we investigated the expression of UP Ia in TCC from patients who had undergone radical cystectomy and from autopsy cases. Positive staining (10% or more positive cancer cells) was noted in primary lesions from 61 of 63 (96.8%) cystectomy patients. Depending on pathological grade, high expression (50% or more positive cancer cells) was observed in 17 of 18 (94.4%) moderately- to well-differentiated TCC and in 36 of 45 (80.0%) poorly differentiated TCC. With regard to tumor invasion, high expression was noted in 20 of 22 (90.9%) superficial and 33 of 41 (80.5%) muscle-invasive TCC. Cause-specific survival rates were 68.6% and 75.0% in high- and low-expression patients, respectively (log-rank test, P=0.855, mean follow-up; 65.0 months). In metastases, positive reactions were observed in 13 of 18 (72.2%) lesions. UP Ia may represent a specific histological marker judging from the stable expression, although its value as a prognostic factor remains undetermined.
REFERENCES
- 1 ) Greenlee , R. T. , Murray , T. , Bolden , S. and Wingo , P. A. Cancer statistics, 2000 . CA Cancer J. Clin. , 50 , 7 – 33 ( 2000 ).
- 2 ) Murphy , W. M. , Beckwith , J. B. and Farrow , G. M. Tumor of the urinary bladder . In “ Atlas of Tumor Pathology. Tumors of the Kidney, Bladder, and Related Urinary Structures ,” ed. J. Rosai and L. H. Sobin , pp. 199 ( 1994 ). Armed Forces Institute of Pathology , Washington , DC .
- 3 ) Yu , J. , Manabe , M. , Wu , X.-R. , Xu , C. , Surya , B. and Sun , T.-T. Uroplakin I: a 27-kD protein associated with the asymmetric unit membrane of mammalian urothelium . J. Cell Biol. , 111 , 1207 – 1216 ( 1990 ).
- 4 ) Yuasa , T. , Yoshiki , T. , Tanaka , T. , Kim , C.-J. , Isono , T. and Okada , Y. Expression of uroplakin Ib and uroplakin III genes in tissues and peripheral blood of patients with transitional cell carcinoma . Jpn. J. Cancer Res. , 89 , 879 – 882 ( 1998 ).
- 5 ) Yuasa , T. , Yoshiki , T. , Isono , T. , Tanaka , T. , Hayashida , H. and Okada , Y. Expression of transitional cell-specific genes, uroplakin Ia and uroplakin II, in bladder cancer: detection of circulating cancer cells in the peripheral blood of metastatic patients . Int. J. Urol. , 6 , 286 – 292 ( 1999 ).
- 6 ) Lu , J.-J. , Kakehi , Y. , Takahashi , T. , Wu , X.-X. , Yuasa , T. , Yoshiki , T. , Okada , Y. , Terachi , T. and Ogawa , O. Detection of circulating cancer cells by reverse transcription-polymerase chain reaction for uroplakin II in peripheral blood of patients with urothelial cancer . Clin. Cancer Res. , 6 , 3166 – 3171 ( 2000 ).
- 7 ) Moll , R. , Wu , X.-R. , Lin , J.-H. and Sun , T.-T. Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas . Am. J. Pathol. , 147 , 1383 – 1397 ( 1995 ).
- 8 ) Kaufmann , O. , Volmerig , J. and Manfred , D. Uroplakin III is a highly specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas . Am. J. Clin. Pathol. , 113 , 683 – 687 ( 2000 ).
- 9 ) Wu , R.-L. , Osman , I. , Wu , X.-R. , Lu , M.-L. , Zhang , Z.-F. , Liang , F.-X. , Hamza , R. , Scher , H. , Cordon-Cardo , C. and Sun , T.-T. 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 . Cancer Res. , 58 , 1291 – 1297 ( 1998 ).
- 10 ) Ogawa , K. , Johansson , S. L. and Cohen , S. M. Immunohistochemical analysis of uroplakins, urothelial specific proteins, in ovarian Brenner tumors, normal tissues, and benign and neoplastic lesions of the female genital tract . Am. J. Pathol. , 155 , 1047 – 1050 ( 1999 ).
- 11 ) Kageyama , S. , Yoshiki , T. , Hamaguchi , A. , Konishi , T. , Okada , Y. , Park , K.-I. and Tomoyoshi , T. Clinical analysis of bladder cancer patients treated by radical cystectomy . Acta Urol. Jpn. , 43 , 1 – 6 ( 1997 ) (in Japanese) .
- 12 ) P. Hermanek and L. H. Sobin , ed. “ UICC-International Union against Cancer TNM Classification of Malignant Tumours ,” 4th Ed. , pp. 135 ( 1987 ). Springer-Verlag , Heidelberg .
- 13 ) Tanaka , T. , Yoshiki , T. , Arai , Y. , Higuchi , K. , Kageyama , S. , Ogawa , Y. , Isono , T. and Okada , Y. Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human bladder cancer . Jpn. J. Cancer Res. , 90 , 1344 – 1350 ( 1999 ).
- 14 ) Yu , J. , Lin , J.-H. , Wu , X.-R. and Sun , T.-T. Uroplakins Ia and Ib, two major differentiation products of bladder epithelium, belong to a family of four transmembrane domain (4TM) proteins . J. Cell Biol. , 125 , 171 – 182 ( 1994 ).
- 15 ) Wu , X.-R. , Lin , J.-H. , Walz , T. , Häner , M. , Yu , J. , Aebi , U. and Sun , T.-T. Mammalian uroplakins. A group of highly conserved urothelial differentiation-related membrane proteins . J. Biol. Chem. , 269 , 13716 – 13724 ( 1994 ).
- 16 ) Adachi , W. , Okubo , K. and Kinoshita , S. Human uroplakin Ib in ocular surface epithelium . Invest. Ophthalmol. Vis. Sci. , 41 , 2900 – 2905 ( 2000 ).
- 17 ) Schaefer , B. M. , Lorenz , C. , Back , W. , Moll , R. , Sun , T.-T. , Schober , C. , Waag , K. L. and Kramer , M. D. Autologous transplantation of urothelium into demucosalized gastrointestinal segments: evidence for epithelialization and differentiation of in vitro expanded and transplanted urothelial cells . J. Urol. , 159 , 284 – 290 ( 1998 ).
- 18 ) Zhang , Z.-T. , Pak , J. , Shapiro , E. , Sun , T.-T. and Wu , X.-R. Urothelium-specific expression of an oncogene in transgenie mice induced the formation of carcinoma in situ and invasive transitional cell carcinoma . Cancer Res. , 59 , 3512 – 3517 ( 1999 ).
- 19 ) Gitlin , J. S. , Wu , X.-R. , Sun , T.-T. , Ritchey , M. L. and Shapiro , E. New concepts of histological changes in experimental augmentation cystoplasty: insights into the development of neoplastic transformation at the enterovesical and gastrovesical anastomosis . J. Urol. , 162 , 1096 – 1100 ( 1999 ).
- 20 ) Ogawa , K. , St John , M. , Luiza de Oliveira , M. , Arnold , L. , Shirai , T. , Sun , T.-T. and Cohen , S. M. Comparison of uroplakin expression during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats and mice . Toxicol. Pathol. , 27 , 645 – 651 ( 1999 ).
- 21 ) Malagolini , N. , Cavallone , D. , Wu , X.-R. and Serafini-Cessi , F. Terminal glycosylation of bovine uroplakin III, one of the major integral-membrane glycoproteins of mammalian bladder . Biochim. Biophys. Acta , 1475 , 231 – 237 ( 2000 ).
- 22 ) Shapiro , E. , Huang , H.-Y. and Wu , X.-R. Uroplakin and androgen receptor expression in the human fetal genital tract: insights into the development of the vagina . J. Urol. , 164 , 1048 – 1051 ( 2000 ).
- 23 ) Wu , X.-R. , Manabe , M. , Yu , J. and Sun , T.-T. Large scale purification and immunolocalization of bovine uroplakins I, II, and III. Molecular markers of urothelial differentiation . J. Biol. Chem. , 265 , 19170 – 19179 ( 1990 ).
- 24 ) Lobban , E. D. , Smith , B. A. , Hall , G. D. , Harnden , P. , Roberts , P. , Selby , P. J. , Trejdosiewicz , L. K. and Southgate , J. Uroplakin gene expression by normal and neoplastic human urothelium . Am. J. Pathol. , 153 , 1957 – 1967 ( 1998 ).
- 25 ) Konety , B. R. , Nguyen , T. S. , Dhir , R. , Day , R. S. , Becich , M. J. , Stadler , W. M. and Getzenberg , R. H. Detection of bladder cancer using a novel nuclear matrix protein, BLCA-4 . Clin. Cancer Res. , 6 , 2618 – 2625 ( 2000 ).