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Präkanzerosen des Urothels

Von der Feulgen-Färbung bis zur Einzelzell-CGH

Precancerous lesions of the urothelium

From Feulgen staining to single cell CGH

  • Schwerpunkt: Uropathologie
  • Published:
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Zusammenfassung

Die Feulgen-Färbung mit der Möglichkeit der quantitativen Wiedergabe der DNA-Menge eines Kerns ist eine gute und einfache Methode, die unregelmäßige DNA-Vermehrung einer malignen Zelle wiederzugeben, welche wiederum Ausdruck der genetischen Instabilität ist. Die genetische Instabilität einer Tumorzelle ist das Kernstück der WHO-Klassifikation des Harnblasenkarzinoms aus dem Jahr 2004, innerhalb derer flache und papilläre Neoplasien in „Low-“ und „High-grade-Läsionen“ eingeteilt werden. „High grade“ gibt die genetische Instabilität und die damit verbundene höhere Progressionswahrscheinlichkeit wieder. Begleitende konkrete genetische Alterationen über die rein numerischen hinaus werden zunehmend diskriminierend identifiziert und zugeordnet. Der Stand der genetischen Untersuchungen insbesondere bei den Präkanzerosen wird hier im Kontext mit Morphologie (histologischer und zytologischer Diagnostik) und Klinik schwerpunktmäßig zusammengefasst.

Abstract

Feulgen staining represents a staining method to quantitatively document the DNA content of a nucleus. Thus it is an excellent and straightforward method to reflect the irregular increase in DNA content of a malignant cell as a sign of genetic instability. Genetic instability of the tumour cell is the key feature of the 2004 WHO classification of bladder tumours, in which flat and papillary neoplasia are grouped into low- and high-grade lesions. “High grade” represents the tumor with genetic instability and consequently a higher likelihood of progression. Concomitant distinct genetic aberrations other than the numeric ones are increasingly identified as discriminators and help group the entities. The current status of genetic investigations, especially those in precancerous lesions, will be outlined in this review in the context of morphology (histology and cytology) as well as clinical situation.

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Literatur

  1. Banks RE, Dunn MJ, Hochstrasser DF et al. (2000) Proteomics: new perspectives, new biomedical opportunities. Lancet 356: 1749–1756

    Article  PubMed  CAS  Google Scholar 

  2. Brassell SA, Kamat AM (2006) Contemporary intravesical treatment options for urothelial carcinoma of the bladder. Review J Natl Compr Canc Netw 10: 1027–1036

    Google Scholar 

  3. Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF-MS. Anal Chem 69: 4751–4760

    Article  PubMed  CAS  Google Scholar 

  4. Celis JE, Gromoy P (2003) Proteomics in translational cancer research: towards an integrated approach. Cancer Cell 3: 9–15

    Article  PubMed  CAS  Google Scholar 

  5. Chaurand P, Sanders ME, Jensen RA, Caprioli RM (2004) Proteomics in diagnostic pathology: profiling and imaging proteins directly in tissue sections. Am J Pathol 165: 1057–1068

    PubMed  CAS  Google Scholar 

  6. Dhawan D, Hamdy FC, Rehman I et al. (2006) Evidence for the early onset of aberrant promoter methylation in urothelial carcinoma. J Pathol 209: 336–343

    Article  PubMed  CAS  Google Scholar 

  7. Dörrenhaus A, Müller T, Roos PH (2007) Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette smokers compared to non-smokers. Arch Toxicol 81: 19–25

    Article  PubMed  CAS  Google Scholar 

  8. Dyrskjøt L, Kruhøffer M, Thykjaer T et al. (2004) Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res 64: 4040–4048

    Article  PubMed  Google Scholar 

  9. Eble JN, Sauter G, Epstsein JI, Sesterhenn IA (eds) (2004) Tumors of the urinary system and male genital tract. WHO classification of tumours. Pathology & genetics. IARC Press, Lyon

  10. Gaisa NT, Donner A, Serenyi S v et al. (2008) Urotheliales Carcinoma in situ der Samenblasen - Ausdruck von Tumor-Multifokalität. Pathologe

  11. Gontijo AM, Marcondes JP, Elias FN et al. (2002) DNA damage in cytologically normal urothelial cells of patients with a history of urothelial cell carcinoma. Environ Mol Mutagen 40: 190–199

    Article  PubMed  CAS  Google Scholar 

  12. Hafner C, Knuechel R, Zanardo L et al. (2001) Evidence for oligoclonality and tumor spread by intraluminal seeding in multifocal urothelial carcinomas of the upper and lower urinary tract. Oncogene 20: 4910–4915

    Article  PubMed  CAS  Google Scholar 

  13. Hanash S (2003) Disease proteomics. Nature 422: 226–232

    Article  PubMed  CAS  Google Scholar 

  14. Herbsleb M, Christensen OF, Thykjaer T et al. (2008) Bioinformatic identification of FGF p38-MAPK and calcium signalling pathways associated with carcinoma in situ in the urinary bladder. BMC Cancer 8: 37. Epub ehead of print

    Article  PubMed  CAS  Google Scholar 

  15. Hofstädter F, Delgado R, Jakse G, Judmaier W (1986) Urothelial dysplasia and carcinoma in situ of the bladder. Cancer 57: 356–361

    Article  PubMed  Google Scholar 

  16. Hungerhuber E, Stepp H, Kriegmair M et al. (2007) Seven years‘ experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder. Urology 69: 260–264

    Article  PubMed  Google Scholar 

  17. Junker K, Boerner D, Schulze W et al. (2003) Analysis of genetic alterations in normal bladder urothelium. Urology 62: 1134–1138

    Article  PubMed  Google Scholar 

  18. Knowles MA (2006) Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Review Carcinogenesis 27: 361–373

    Article  CAS  Google Scholar 

  19. Knowles MA (2008) Novel therapeutic targets in bladder cancer: mutation and expression of FGF receptors. Review Future Oncol 4: 71–83

    Article  CAS  Google Scholar 

  20. Knüchel R, Hartmann A, Stöhr R et al. (2003) Präkanzerosen des Urothels. Früherkennung und molekulares Verständnis durch endoskopische Fluoreszenzdiagnostik. Pathologe 24: 473–479

    Article  PubMed  Google Scholar 

  21. Koufou S, Langer SK, Lindemann-Docter K et al. (2006) Investigation of genetic aberrations in precancerous lesions of the bladder by double staining of fluroescence in situ hybridization and Ki-67 immunohistochemistry and by comparative genomic hybridisation. Path Res Pract 202: 337

    Google Scholar 

  22. Moore LE, Pfeiffer RM, Poscablo C et al. (2008) Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the spanish bladder cancer study: a case-control study. Lancet Oncol Epub ahead of print

  23. Murta-Nascimento C, Schmitz-Dräger BJ, Zeegers MP et al. (2007) Epidemiology of urinary bladder cancer: from tumor development to patient’s death. World J Urol 25: 285–295

    Article  PubMed  Google Scholar 

  24. Neuhausen A, Florl AR, Grimm MO, Schulz WA (2006) DNA methylation alterations in urothelial carcinoma. Cancer Biol Ther 5: 993–1001

    Article  PubMed  CAS  Google Scholar 

  25. Pelucchi C, Bosetti C, Negri E et al. (2006) Mechanisms of disease: the epidemiology of bladder cancer. Nat Clin Pract Urol 3: 327–340

    Article  PubMed  CAS  Google Scholar 

  26. Schwarz S, Rechenmacher M, Filbeck T et al. (2008) Value of multicolour fluorescence in situ hybridisation (UroVysion) in the differential diagnosis of flat urothelial lesions. J Clin Pathol 3: 272–277

    Google Scholar 

  27. Stoehr R, Zietz S, Burger M et al. (2005) Deletions of chromosomes 9 and 8p in histologically normal urothelium of patients with bladder cancer. Eur Urol 47: 58–63

    Article  PubMed  CAS  Google Scholar 

  28. Stoehr R, Hartmann A (2007) Histopathologie und Molekulargenetik des Harnblasenkarzinoms. Onkologe 12: 1058–1066

    Article  Google Scholar 

  29. van Oers JM, Adam C, Denzinger S et al. (2006) Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial hyperplasias of the bladder. Int J Cancer 119: 1212–1215

    Article  CAS  Google Scholar 

  30. Zaak D, Karl A, Knüchel R et al. (2005) Diagnosis of urothelial carcinoma of the bladder using fluorescence endoscopy. BJU International 96: 217–222

    Article  PubMed  Google Scholar 

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Danksagung

Die hier geschilderten Arbeiten wurden z. T. mit Forschungsgeldern der DFG gefördert: KN263 9–2, Sp 460/5–2.

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Knüchel-Clarke, R., Koufou, S., Speicher, M. et al. Präkanzerosen des Urothels. Pathologe 29, 364–370 (2008). https://doi.org/10.1007/s00292-008-1015-1

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  • DOI: https://doi.org/10.1007/s00292-008-1015-1

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