Molekulare Marker in Diagnostik und Therapie des Urothelkarzinoms
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Zusammenfassung
Bei zahlreichen klinischen Entscheidungen in der Behandlung des Blasenkarzinoms wäre es hilfreich, genauere Kenntnis über die Prognose des individuellen Tumors zu haben. Marker für das Urothelkarzinom können dabei im peripheren Blut, im Urin und im transurethral resezierten Gewebe bestimmt werden. Zahlreiche Entwicklungen haben zur Kenntnis neuer Marker geführt. Da kein einzelner Marker im Sinne einer Schwarz-Weiß-Entscheidung aussagekräftig ist, sondern immer nur ein Mehr oder Weniger an Wahrscheinlichkeit resultiert, hat sich der klinische Einsatz der Marker insgesamt bislang nicht grundlegend durchgesetzt, wobei sich dies in Zukunft ändern könnte.
Schlüsselwörter
Blasenkarzinom Tumorprogression Urin Genetik TumormarkerMolecular markers in the diagnostics and therapy of urothelial cancer
Abstract
Many clinical decisions in the management of bladder cancer would benefit from better and reliable knowledge of individual prognosis. Marker for urothelial cancer can principally be measured in blood, urine and transurethrally resected tissue. In recent years new markers have been identified by new technologies and this opens exiting avenues. Since no single marker gives a clear Yes-or-no prognostic answer but always only a measure of probability, the use of marker systems has so far not gained widespread clinical applications. This will likely change in future.
Keywords
Urinary bladder cancer Disease progression Urine Genetics Tumor markers, biologicalNotes
Interessenkonflikt
Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.
Literatur
- 1.Ries LAG, Melbert D, Krapcho M et al (2008) SEER cancer statistics review, 1975–2005. National cancer institut, bethesda. Based on November 2007 SEER data submission, posted to the SEER websiteGoogle Scholar
- 2.Nezos A, Pissimisis N, Lembessis P et al (2009) Detection of circulating tumor cells in bladder cancer patients. Cancer Treat Rev 35(3):272–279CrossRefPubMedGoogle Scholar
- 3.Cristofanilli M, Budd GT, Ellis MJ et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791CrossRefPubMedGoogle Scholar
- 4.Keilholz U, Willhauck M, Rimoldi D et al (1998) Reliability of reverse transcription-polymerase chain reaction (RT-PCR)-based assays for the detection of circulating tumour cells: a quality-assurance initiative of the EORTC Melanoma Cooperative Group. Eur J Cancer 34(5):750–753CrossRefPubMedGoogle Scholar
- 5.Kaneda T, Hoshi S, Mao H et al (1998) Detection of urogenital malignant cells in the peripheral blood by nested RT-PCR using keratin 19 mRNA. Nippon Hinyokika Gakkai Zasshi 89(1):33–42PubMedGoogle Scholar
- 6.Alvarez A, Lokeshwar VB (2007) Bladder cancer biomarkers: current developments and future implementation. Curr Opin Urol 17(5):341–346CrossRefPubMedGoogle Scholar
- 7.Lokeshwar VB, Selzer MG (2006) Urinary bladder tumor markers. Urol Oncol 24(6):528–537PubMedGoogle Scholar
- 8.Schultz IJ, Witjes JA, Swinkels DW et al (2006) Bladder cancer diagnosis and recurrence prognosis: comparison of markers with emphasis on survivin. Clin Chim Acta 368(1–2):20–32Google Scholar
- 9.McKenney JK, Amin MB (2005) The role of immunohistochemistry in the diagnosis of urinary bladder neoplasms. Semin Diagn Pathol 22(1):69–87CrossRefPubMedGoogle Scholar
- 10.Yuasa T, Yoshiki T, Isono T et al (1999) Expression of transitional cell-specific genes, uroplakin Ia and II, in bladder cancer: detection of circulating cancer cells in the peripheral blood of metastatic patients. Int J Urol 6(6):286–292CrossRefPubMedGoogle Scholar
- 11.Osman I, Kang M, Lee A et al (2004) Detection of circulating cancer cells expressing uroplakins and epidermal growth factor receptor in bladder cancer patients. Int J Cancer 111(6):934–939CrossRefPubMedGoogle Scholar
- 12.Li SM, Zhang ZT, Chan S et al (1999) Detection of circulating uroplakin-positive cells in patients with transitional cell carcinoma of the bladder. J Urol 162(3 Pt 1):931–935CrossRefPubMedGoogle Scholar
- 13.Lu JJ, Kakehi Y, Takahashi T et al (2000) 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(8):3166–3171PubMedGoogle Scholar
- 14.Retz M, Lehmann J, Röder C et al (2001) Cytokeratin-20 reverse-transcriptase polymerase chain reaction as a new tool for the detection of circulating tumor cells in peripheral blood and bone marrow of bladder cancer patients. Eur Urol 39(5):507–515; discussion 516–517CrossRefPubMedGoogle Scholar
- 15.Kinjo M, Okegawa T, Horie S et al (2004) Detection of circulating MUC7-positive cells by reverse transcription-polymerase chain reaction in bladder cancer patients. Int J Urol 11(1):38–43CrossRefPubMedGoogle Scholar
- 16.Gazzaniga P, Gandini O, Giuliani L et al (2001) Detection of epidermal growth factor receptor mRNA in peripheral blood: a new marker of circulating neoplastic cells in bladder cancer patients. Clin Cancer Res 7(3):577–583PubMedGoogle Scholar
- 17.Gradilone A, Petracca A, Nicolazzo C et al (2010) Prognostic significance of survivin-expressing circulating tumour cells in T1G3 bladder cancer. BJU Int [Epub ahead of print]Google Scholar
- 18.Okegawa T, Kinjo M, Nutahara K et al (2004) Value of reverse transcription polymerase chain assay in peripheral blood of patients with urothelial cancer. J Urol 171(4):1461–1466CrossRefPubMedGoogle Scholar
- 19.Osman I, Bajorin DF, Sun TT et al (2006) Novel blood biomarkers of human urinary bladder cancer. Clin Cancer Res 12(11 Pt 1):3374–3380CrossRefPubMedGoogle Scholar
- 20.Fraser RA, Ravry MJ, Segura JW et al (1975) Clinical evaluation of urinary and serum carcinoembryonic antigen in bladder cancer. J Urol 114(2):226–229PubMedGoogle Scholar
- 21.Saied GM, El-Metenawy WH, Elwan MS et al (2007) Urine carcinoembryonic antigen levels are more useful than serum levels for early detection of Bilharzial and non-Bilharzial urinary bladder carcinoma: observations of 43 Egyptian cases. World J Surg Oncol 5:4CrossRefPubMedGoogle Scholar
- 22.Kouba EJ, Lentz A, Wallen EM et al (2009) Clinical use of serum CA-125 levels in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder. Urol Oncol 27(5):486–490PubMedGoogle Scholar
- 23.Andreadis C, Touloupidis S, Galaktidou G et al (2005) Serum CYFRA 21–1 in patients with invasive bladder cancer and its relevance as a tumor marker during chemotherapy. J Urol 174(5):1771–1775; discussion 1775–1776CrossRefPubMedGoogle Scholar
- 24.Margel D, Tal R, Baniel J (2007) Serum tumor markers may predict overall and disease specific survival in patients with clinically organ confined invasive bladder cancer. J Urol 178(6):2297–2300; discussion 2300–2301CrossRefPubMedGoogle Scholar
- 25.Sakaki M, Oka N, Nakanishi R et al (2008) Serum level of galectin-3 in human bladder cancer. J Med Invest 55(1–2):127–132Google Scholar
- 26.Malviya V, Singh H, Dwivedi US et al (2004) Serum p53 and bladder cancer: can serum p53 be used as a tumor marker? Urol Res 32(6):391–394CrossRefPubMedGoogle Scholar
- 27.Mizutani Y, Matsubara H, Yamamoto K et al (2004) Prognostic significance of serum osteoprotegerin levels in patients with bladder carcinoma. Cancer 101(8):1794–1802CrossRefPubMedGoogle Scholar
- 28.Hazzaa SM, Elashry OM, Afifi IK (2010) Clusterin as a diagnostic and prognostic marker for transitional cell carcinoma of the bladder. Pathol Oncol Res 16(1):101–109CrossRefPubMedGoogle Scholar
- 29.Takata R, Obara W, Fujioka T (2010) Study of the prediction system for clinical response to M-VAC neoadjuvant chemotherapy for bladder cancer. Aktuelle Urol 41(Suppl 1):S41–S45CrossRefPubMedGoogle Scholar
- 30.Protzel C, Hakenberg OW (2009) Emerging apoptosis agonists for bladder cancer. Expert Opin Emerg Drugs 14(4):607–618CrossRefPubMedGoogle Scholar
- 31.Vrooman OP, Witjes JA (2009) Molecular markers for detection, surveillance and prognostication of bladder cancer. Int J Urol 16(3):234–243CrossRefPubMedGoogle Scholar
- 32.Coleman JF, Hansel DE (2009) Utility of diagnostic and prognostic markers in urothelial carcinoma of the bladder. Adv Anat Pathol 16(2):67–78CrossRefPubMedGoogle Scholar
- 33.Billerey C, Chopin D, Aubriot-Lorton MH et al (2001) Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol 158(6):1955–1959PubMedGoogle Scholar
- 34.Rhijn BW van, Lurkin I, Radvanyi F et al (2001) The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res 61(4):1265–1268PubMedGoogle Scholar
- 35.Holmang S, Andius P, Hedelin H et al (2001) Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy. J Urol 165(4):1124–1128; discussion 1128–1130CrossRefPubMedGoogle Scholar
- 36.Lopez-Knowles E, Hernández S, Malats N et al (2006) PIK3CA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. Cancer Res 66(15):7401–7404CrossRefPubMedGoogle Scholar
- 37.Mengual L, Burset M, Ars E et al (2009) DNA microarray expression profiling of bladder cancer allows identification of noninvasive diagnostic markers. J Urol 182(2):741–748CrossRefPubMedGoogle Scholar
- 38.Bakkar AA, Wallerand H, Radvanyi F et al (2003) FGFR3 and TP53 gene mutations define two distinct pathways in urothelial cell carcinoma of the bladder. Cancer Res 63(23):8108–8112PubMedGoogle Scholar
- 39.Desai S, Lim SD, Jimenez RE et al (2000) Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia. Mod Pathol 13(12):1315–1323CrossRefPubMedGoogle Scholar
- 40.McKenney JK, Desai S, Cohen C et al (2001) Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens. Am J Surg Pathol 25(8):1074–1078CrossRefPubMedGoogle Scholar
- 41.Limas C, Bigler A, Bair R et al (1993) Proliferative activity of urothelial neoplasms: comparison of BrdU incorporation, Ki67 expression, and nucleolar organiser regions. J Clin Pathol 46(2):159–165CrossRefPubMedGoogle Scholar
- 42.Garcia del Muro X, Torregrosa A, Muñoz J et al (2000) Prognostic value of the expression of E-cadherin and beta-catenin in bladder cancer. Eur J Cancer 36(3):357–362CrossRefGoogle Scholar
- 43.Rabbani F, Koppie TM, Charytonowicz E et al (2007) Prognostic significance of p27Kip1 expression in bladder cancer. BJU Int 100(2):259–263CrossRefPubMedGoogle Scholar
- 44.Swana HS, Grossman D, Anthony JN et al (1999) Tumor content of the antiapoptosis molecule survivin and recurrence of bladder cancer. N Engl J Med 341(6):452–453CrossRefPubMedGoogle Scholar
- 45.Shariat SF, Ashfaq R, Karakiewicz PI et al (2007) Survivin expression is associated with bladder cancer presence, stage, progression, and mortality. Cancer 109(6):1106–1113CrossRefPubMedGoogle Scholar
- 46.Lu ML, Wikman F, Orntoft TF et al (2002) Impact of alterations affecting the p53 pathway in bladder cancer on clinical outcome, assessed by conventional and array-based methods. Clin Cancer Res 8(1):171–179PubMedGoogle Scholar
- 47.Shariat SF, Ashfaq R, Sagalowsky AI et al (2006) Correlation of cyclin D1 and E1 expression with bladder cancer presence, invasion, progression, and metastasis. Hum Pathol 37(12):1568–1576CrossRefPubMedGoogle Scholar
- 48.Karam JA, Lotan Y, Ashfaq R et al (2007) Survivin expression in patients with non-muscle-invasive urothelial cell carcinoma of the bladder. Urology 70(3):482–486CrossRefPubMedGoogle Scholar
- 49.Gonzalez S, Aubert S, Kerdraon O et al (2008) Prognostic value of combined p53 and survivin in pT1G3 urothelial carcinoma of the bladder. Am J Clin Pathol 129(2):232–237CrossRefPubMedGoogle Scholar
- 50.Sanchez-Carbayo M, Socci ND, Lozano JJ et al (2003) Gene discovery in bladder cancer progression using cDNA microarrays. Am J Pathol 163(2):505–516PubMedGoogle Scholar
- 51.Catto JW, Abbod MF, Wild PJ et al (2010) The application of artificial intelligence to microarray data: identification of a novel gene signature to identify bladder cancer progression. Eur Urol 57(3):398–406CrossRefPubMedGoogle Scholar
- 52.Williams PD et al (2009) Concordant gene expression signatures predict clinical outcomes of cancer patients undergoing systemic therapy. Cancer Res 69(21):8302–8309CrossRefPubMedGoogle Scholar
- 53.Britton JP, Cheon S, Havaleshko DM et al (1992) A community study of bladder cancer screening by the detection of occult urinary bleeding. J Urol 148(3):788–790PubMedGoogle Scholar
- 54.Messing EM, Young TB, Hunt VB et al (1992) Home screening for hematuria: results of a multiclinic study. J Urol 148(2 Pt 1):289–292PubMedGoogle Scholar
- 55.Messing EM, Madeb R, Young T et al (2006) Long-term outcome of hematuria home screening for bladder cancer in men. Cancer 107(9):2173–2179CrossRefPubMedGoogle Scholar
- 56.Konety B, Lotan Y (2008) Urothelial bladder cancer: biomarkers for detection and screening. BJU Int 102(9 Pt B):1234–1241CrossRefPubMedGoogle Scholar
- 57.Lotan Y, Elias K, Svatek RS et al (2009) Bladder cancer screening in a high risk asymptomatic population using a point of care urine based protein tumor marker. J Urol 182(1):52–57; discussion 58CrossRefPubMedGoogle Scholar
- 58.Steiner H, Bergmeister M, Verdorfer I et al (2008) Early results of bladder-cancer screening in a high-risk population of heavy smokers. BJU Int 102(3):291–296CrossRefPubMedGoogle Scholar
- 59.Roobol MJ, Zwarthoff EC Franken-Raab CGAM et al (2009) Feasibility study of population based screening for bladder cancer with urinary molecular markers (BLUP). Eur Urol Suppl 8:151CrossRefGoogle Scholar
- 60.Rhijn BW van, Poel HG van der, Kwast TH van der (2005) Urine markers for bladder cancer surveillance: a systematic review. Eur Urol 47(6):736–748CrossRefPubMedGoogle Scholar
- 61.Mian C, Maier K, Comploj E et al (2006) UCyt+∕ImmunoCyt in the detection of recurrent urothelial carcinoma: an update on 1991 analyses. Cancer 108(1):60–65CrossRefPubMedGoogle Scholar
- 62.Messing EM, Teot L, Korman H et al (2005) Performance of urine test in patients monitored for recurrence of bladder cancer: a multicenter study in the United States. J Urol 174(4 Pt 1):1238–1241CrossRefPubMedGoogle Scholar
- 63.Gudjonsson S, Isfoss BL, Hansson K et al (2008) The value of the UroVysion assay for surveillance of non-muscle-invasive bladder cancer. Eur Urol 54(2):402–408CrossRefPubMedGoogle Scholar
- 64.Zwarthoff EC (2008) Detection of tumours of the urinary tract in voided urine. Scand J Urol Nephrol Suppl (218):147–153CrossRefGoogle Scholar
- 65.Vrooman OP, Witjes JA (2008) Urinary markers in bladder cancer. Eur Urol 53(5):909–916CrossRefPubMedGoogle Scholar
- 66.Mengual L, Marín-Aguilera M, Ribal MJ et al (2007) Clinical utility of fluorescent in situ hybridization for the surveillance of bladder cancer patients treated with bacillus Calmette-Guerin therapy. Eur Urol 52(3):752–759CrossRefPubMedGoogle Scholar
- 67.Grossman HB, Soloway M, Messing E et al (2006) Surveillance for recurrent bladder cancer using a point-of-care proteomic assay. JAMA 295(3):299–305CrossRefPubMedGoogle Scholar
- 68.Gupta NP, Sharma N, Kumar R (2009) Nuclear matrix protein 22 as adjunct to urine cytology and cystoscopy in follow-up of superficial TCC of urinary bladder. Urology 73(3):592–596; discussion 596–597CrossRefPubMedGoogle Scholar