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Prognostic value of keratin subtyping in transitional cell carcinoma of the upper urinary tract

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Abstract

To investigate the prognostic value of keratin subtyping in invasive transitional cell carcinomas (TCCs), we performed a systematic study applying 15 different monoclonal keratin antibodies on 53 upper urinary tract TCCs using a tissue microarray technique. Immunoreactivity was correlated with pT stages and tumour grades using the Fisher’s exact test. Impact on disease-free survival was analysed using the Kaplan-Meier method and compared by the log-rank test. Immunoreactivity for keratins 5/6, 6, 7, 8, 13, 14, 17, 18, 19, 20, low molecular weight (LMW) keratins (8, 18) and high molecular weight (HMW) keratins (1, 5, 10, 14) was detected in varying quantities. Regarding semi-quantitative assessment, a prognostic impact was found for keratins 5/6, 7, 8, 13, 17, 20 and HMW keratins, with reduced expression or loss of immunoreactivity being significantly associated with disease progression. With respect to analysis of staining patterns, the retention of a basally accentuated labelling for keratin 5/6 and HMW keratin as well as a superficially accentuated labelling for keratin 20 was significantly associated with a favourable outcome. In conclusion, this investigation is the first to demonstrate a possible prognostic value for keratin subtyping in invasive (upper urinary tract) TCCs with respect to metastasis-free survival. Further studies, however, are needed to substantiate our results.

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References

  1. Alsheikh A, Mohamedali Z, Jones E, Masterson J, Gilks CB (2001) Comparison of the WHO/ISUP classification and cytokeratin 20 expression in predicting the behaviour of low-grade papillary urothelial tumors. Mod Pathol 14:267–272

    Article  CAS  PubMed  Google Scholar 

  2. Bhatavdekar JM, Patel DD, Chikhlikar PR, Shah NG, Vora HH, Ghosh N, Trivedi TI (2001) Molecular markers are predictors of recurrence and survival in patients with Dukes B and Dukes C colorectal adenocarcinoma. Dis Colon Rectum 44:523–533

    CAS  PubMed  Google Scholar 

  3. Bommel van PF, Kenemans P, Helmerhorst TJM, Gallee MPW, Ivanyi D (1994) Expression of cytokeratin 10, 13, and in involucrin as prognostic factors in low stage squamous cell carcinoma of the uterine cervix. Cancer 74:2314–2320

    PubMed  Google Scholar 

  4. Chu PG, Weiss LM (2002) Expression of cytokeratin 5/6 in epithelial neoplasms: an immunohistochemical study of 509 cases. Mod Pathol 15:6–10

    Article  PubMed  Google Scholar 

  5. Chu PG, Weiss LM (2002) Keratin expression in human tissues and neoplasms. Histopathology 40:403–439

    Article  CAS  PubMed  Google Scholar 

  6. Chu PG, Wu E, Weiss LM (2000) Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 13:962–972

    Article  CAS  PubMed  Google Scholar 

  7. Chu PG, Lyda MH, Weiss LM (2001) Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours. Histopathology 39:9–16

    Article  CAS  PubMed  Google Scholar 

  8. Cintorino M, Tripod SA, Santopietro R, Antonio P, Lutfi A, Chang F, Syrjanen S, Shen Q, Tosi P, Syrjanen K (2001) Cytokeratin expression patterns as an indicator of tumour progression in oesophageal squamous cell carcinoma. Anticancer Res 21:4195–4201

    CAS  PubMed  Google Scholar 

  9. Cohen R, Guber A, Siegal A, Brudermamn I, Huszar M, Yellin A, Marom Z, Geiger B (1997) The prognostic application of cytokeratin typing of nonsmall cell ling carcinoma. A retrospective study. Cancer 79:468–473

    Article  CAS  PubMed  Google Scholar 

  10. Depondt J, Shabana AH, Sawaf H, Gehanno P, Forest N (1999) Cytokeratin alterations as diagnostic and prognostic markers of oral and pharyngeal carcinomas. A prospective study. Eur J Oral Sci 107:442–454

    Article  CAS  PubMed  Google Scholar 

  11. Genega EM, Porter CR (2002) Urothelial neoplasm of the kidney and ureter. An epidemiologic, pathologic, and clinical review. Am J Clin Pathol 117[Suppl]:S36–S48

  12. Guelstein VI, Tchipysheva TA, Ermilova VD, Troyanovsky SM (1993) Immunohistochemical localization of cytokeratin 17 in transitional cell carcinomas of the human urinary tract. Virchows Arch 64:1–5

    CAS  Google Scholar 

  13. Hall MC, Womack S, Sagalowsky AI (1998) Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology 52:594–601

    Article  CAS  PubMed  Google Scholar 

  14. Harnden P, Parkinson MC (1996) Transitional cell carcinoma of the bladder: diagnosis and prognosis. Curr Diagn Pathol 3:109–121

    Google Scholar 

  15. Harnden P, Southgate J (1997) Cytoketain 14 as a marker of squamous differentiation in transitional cell carcinomas. J Clin Pathol 50:1032–1033

    CAS  PubMed  Google Scholar 

  16. Harnden P, Allam A, Joyce AD, Patel A, Selby P, Southgate J (1995) Cytokeratin 20 expression by non-invasive transitional cell carcinomas: potential for distinguishing recurrent from non-recurrent disease. Histopathology 27:169–174

    CAS  PubMed  Google Scholar 

  17. Harnden P, Mahmood N, Southgate J (1999) Expression of cytokeratin 20 redefines urothelial papillomas of the bladder. Lancet 353:974–977

    Article  CAS  PubMed  Google Scholar 

  18. Helpap B, Köllermann J (1999) Proliferative pattern of exophytic and superficially invasive and non-invasive low-grade urothelial carcinomas. Hum Pathol 30:145–150

    Article  CAS  PubMed  Google Scholar 

  19. Helpap B, Köllermann J (2000) Assessment of basal cell status and proliferative in flat and papillary urothelial lesions: a contribution to the new WHO classification of urothelial tumors of the bladder. Hum Pathol 31:745–750

    CAS  PubMed  Google Scholar 

  20. Helpap B, Schmitz-Dräger BJ, Hamilton PW, Muzzonigro G, Galosi AB, Kurth KH, Lubaroff D, Waters DJ, Droller MJ (2003) Molecular pathology of non-invasive urothelial carcinoma (part I). Virchows Arch 442:309–316

    CAS  PubMed  Google Scholar 

  21. Kaufmann O, Fietze E, Mengs J, Dietel M (2001) Value of p63 and cytokeratin 5/6 as immunohsitochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol 116:823–830

    Article  CAS  PubMed  Google Scholar 

  22. Kim K, Kim S (2002) Immunohistochemical profile of common epithelial neoplasms arising in the kidney. Appl Immunohistochem Mol Morphol 10:332–338

    Article  CAS  PubMed  Google Scholar 

  23. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847

    CAS  PubMed  Google Scholar 

  24. Langner C, Wegscheider BJ, Ratschek M, Schips L, Zigeuner R (2004) Keratin immunohistochemistry in renal cell carcinoma subtypes and renal oncocytomas: a systematic analysis of 233 tumors. Virchows Arch 444:127–134

    Article  CAS  PubMed  Google Scholar 

  25. Lopez-Beltran A, Sauter G, Gasser T, Hartmann A, Schmitz-Dräger BJ, Helpap B, Ayala AG, Tamboli P, Knwles MA, Sidransky D, Cordon-Cardo C, Jones PA, Cairns P, Simon R, Amin MB, Tyczynski JE (2004) Tumours of the urinary system. Infiltrating urothelial carcinoma. In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds) World Health Organization classification of tumours. Pathology and genetics. Tumours of the urinary system and male genital organs. IARC Press, Lyon pp 93–109

  26. Miettinen M (1995) Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas. Mod Pathol 8:384–388

    CAS  PubMed  Google Scholar 

  27. Moll R (1998) Cytokeratins as markers of differentiation in the diagnosis of epithelial tumors. Subcell Biochem 31:205–262

    CAS  PubMed  Google Scholar 

  28. Moll R, Achtstätter T, Becht E, Balcarova-Ständer J, Ittensohn M, Franke WW (1988) Cytokeratins in normal and malignant transitional epithelium. Maintenance of expression of urothelial differentiation features in transitional cell carcinomas and bladder carcinomas and bladder carcinoma cell culture lines. Am J Pathol 132:123–144

    CAS  PubMed  Google Scholar 

  29. Moll R, Löwe A, Laufer J, Franke WW (1992) Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol 140:427–447

    CAS  PubMed  Google Scholar 

  30. Parker DC, Folpe AL, Bell J, Oliva E, Young RH, Cohen C, Amin MB (2003) Potential utility of uroplakin III, thrombomodulin, high molecular weight cytokeratin and cytokeratin 20 in non-invasive, invasive, and metastatic urothelial (transitional cell) carcinomas. Am J Surg Pathol 27:1–10

    Article  PubMed  Google Scholar 

  31. Ramos D, Navarro S, Villamon R, Gil-Salom M, Llombart-Bosch A (2003) Cytokeratin expression patterns in low-grade papillary urothelial neoplasms of the urinary bladder. Cancer 97:1876–1883

    Article  PubMed  Google Scholar 

  32. Rijn van de M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, Torhorst J, Sauter G, Zuber M, Köchli OR, Mross F, Dieterich H, Seitz R, Ross D, Botstein D, Brown P (2002) Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 161:1991–1996

    PubMed  Google Scholar 

  33. Schaafsma HE, Ramaekers FCS, Muijen van GNP, Lane EB, Leigh IM, Robben H, Huijsmans A, Ooms ECM, Ruiter DJ (1990) Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing patterns during tumour progression. Am J Pathol 136:329–343

    CAS  PubMed  Google Scholar 

  34. Schaafsma HE, Ramaekers FCS, Muijen van GNP, Robben H, Lane EB, Leigh IM, Ooms ECM, Schalken JA, Morselaar van RJA, Ruiter DJ (1991) Cytokeratin expression patterns in metastatic transitional cell carcinoma of the urinary tract. An immunohistochemical study comparing local tumor and autologous metastases. Am J Pathol 139:1389–1400

    CAS  PubMed  Google Scholar 

  35. Schaller G, Fuchs I, Pritze W, Ebert A, Herbst H, Pantel K, Weitzel H, Lengyel E (1996) Elevated keratin 18 protein expression indicates a favourable prognosis in patients with breast cancer. Clin Cancer Res 2:1879–1885

    CAS  PubMed  Google Scholar 

  36. Sobin LH, Wittekind C (eds) (2002) TNM classification of malignant tumors, 6th edn. Wiley-Liss, Inc., New York

  37. Southgate J, Harnden P, Trejdosiewicz LK (1999) Cytokeratin expression patterns in normal and malignant urothelium: a review of the biological and diagnostic implications. Histol Histopathol 14:657–664

    CAS  PubMed  Google Scholar 

  38. Takei H, Iino Y, Horiguchi J, Kanoh T, Takao Y, Oyama T, Morishita Y (1995) Immunohistochemical analysis of cytokeratin 8 as a prognostic factor in invasive breast carcinoma. Anticancer Res 15:1101–1105

    CAS  PubMed  Google Scholar 

  39. Wang NP, Zee S, Zarbo RJ, Bacchi CE, Gown AM (1995) Coordinate expression of cytokeratins 7 and 20 defines unique subsets of carcinomas. Appl Immunohistochem 3:99–107

    Google Scholar 

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Acknowledgements

The authors are grateful to Mrs. M. Gogg-Kamerer, Ms. M. Lindbauer, Ms. A. Sommersacher, Mr. M. Al-Effah and Mr. R. Christof for excellent technical assistance.

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Authors and Affiliations

  1. Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036, Graz, Austria

    Cord Langner, Beate J. Wegscheider & Manfred Ratschek

  2. Department of Surgery, Division of Biomedical Engineering & Computing, Medical University of Graz, Auenbruggerplatz 29, 8036, Graz, Austria

    Peter Rehak

  3. Department of Urology, Medical University of Graz, Auenbruggerplatz 7, 8036, Graz, Austria

    Richard Zigeuner

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  1. Cord Langner
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  2. Beate J. Wegscheider
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Correspondence to Cord Langner.

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Langner, C., Wegscheider, B.J., Rehak, P. et al. Prognostic value of keratin subtyping in transitional cell carcinoma of the upper urinary tract. Virchows Arch 445, 442–448 (2004). https://doi.org/10.1007/s00428-004-1088-z

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  • DOI: https://doi.org/10.1007/s00428-004-1088-z

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