Regular Article

British Journal of Cancer (1999) 81, 6–12. doi:10.1038/sj.bjc.6690643 www.bjcancer.com
Published online 13 August 1999

Cytogenetic monoclonality in multifocal uroepithelial carcinomas: evidence of intraluminal tumour seeding

I Fadl-Elmula1,3, L Gorunova1, N Mandahl1, P Elfving2, R Lundgren3, F Mitelman1 and S Heim4

  1. 1Department of Clinical Genetics University Hospital, S-221 85, Lund, Sweden
  2. 2Department of Urology, University Hospital, S-251 87, Lund, Sweden
  3. 3Department of Urology, Helsingborg Hospital, S-251 87, Helsingborg, Sweden
  4. 4Department of Genetics, The Norwegian Radium Hospital and Institute for Cancer Research, N-0310, Oslo, Norway

Correspondence: I Fadl-Elmula, Department of Clinical Genetics, University Hospital, S-221 85 Lund, Sweden

Received 13 October 1998; Revised 16 February 1999; Accepted 15 March 1999.

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Abstract

Twenty-one multifocal urinary tract transitional cell carcinomas, mostly bladder tumours, from a total of six patients were processed for cytogenetic analysis after short-term culturing of the tumour cells. Karyotypically related, often identical, cytogenetically complex clones were found in all informative tumours from each case, including the recurrent tumours. Rearrangement of chromosome 9, leading to loss of material from the short and/or the long arm, was seen in all cases, indicating that this is an early, pathogenetically important event in transitional cell carcinogenesis. The presence of related clones with great karyotypic similarity in anatomically distinct tumours from the same bladder indicates that multifocal uroepithelial tumours have a monoclonal origin and arise via intraluminal seeding of viable cancer cells shed from the original tumour. Later lesions may develop also from cells shed from the so called second primary tumours. The relatively complex karyotypes seen in all lesions from most cases argue that the seeding of tumour cells is a late event that succeeds the acquisition by them of multiple secondary genetic abnormalities.

Keywords:

cytogenetics, multifocal uroepithelial carcinomas, monoclonality, intraluminal seeding

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References

  1. Badalament, RA & Schervish, EW (1996). Bladder cancer, current diagnostic methods and treatment options. Postgrad Med 100: 217–230.
  2. Breul, J, Block, T, Breidenbach, H & Hartung, R (1992). Implantation metastasis after a suprapubic catheter in a case of bladder cancer. Eur Urol 22: 86–88.
  3. Chern, HD, Becich, MJ, Persad, RA, Romkes, M, Smith, P, Collins, C, Li, YH & Branch, RA (1996). Clonal analysis of human recurrent superficial bladder cancer by immunohistochemistry of p53 and retinoblastoma proteins. J Urol 156: 1846–1849. | Article | PubMed | ISI |
  4. Fadl-Elmula, I, Gorunova, L, Lundgren, R, Mandahl, N, Forsby, N, Mitelman, F & Heim, S (1998). Chromosomal abnormalities in two bladder carcinomas with secondary squamous cell differentiation. Cancer Genet Cytogenet 102: 125–130.
  5. Fitzpatrick, JM, West, AB & Butler, MR (1986). Superficial bladder tumors (stage pTa grade 1 and 2). The importance of recurrence pattern following initial resection. J Urol 135: 920–922.
  6. Fujimoto, K, Yamada, Y, Okajima, E, Kakizoe, T, Sasaki, H, Sugimura, T & Terada, M (1992). Frequent association of p53 gene mutation in invasive bladder cancer. Cancer Res 52: 1393–1398. | PubMed | ISI | ChemPort |
  7. Garden, RJ, Liu, BC & Redwood, SM (1992). Bacillus Calmette-Guerin (BCG) abrogates in vitro invasion and motility of human bladder tumor cell via fibronectin interactions. J Urol 148: 900–950.
  8. Gibas, Z & Gibas, L (1997). Cytogenetics of bladder cancer. Cancer Genet Cytogenet 95: 108–115.
  9. Grossfeld, GD, Ginsberg, DA, Stein, JP, Bochner, BH, Esrig, D, Groshen, S, Dunn, M, Nichols, PW, Taylor, CR, Skinner, DG & Cote, RJ (1997). Thrombospondin-1 expression in bladder cancer: association with TP53 alterations, tumor angiogenesis, and tumor progression. J Natl Cancer Inst 89: 219–227. | Article | PubMed | ChemPort |
  10. Habuchi, T, Takahashi, R, Yamada, H, Kakehi, Y, Sugiyama, T & Yoshida, O (1993). Metachronous multifocal development of urothelial cancers by intraluminal seeding. Lancet 342: 1087–1088. | Article | PubMed | ISI | ChemPort |
  11. Harris, AL & Neal, DE (1992). Bladder cancer, field versus clonal origin. N Engl J Med 326: 759–761. | PubMed | ISI | ChemPort |
  12. Heim, S (1992). Is cancer cytogenetics reducible to the molecular genetics of cancer cells?. Genes Chromosomes Cancer 5: 188–196. | PubMed |
  13. Heney, NM, Proppe, K, Prout, GR, Griffin, PP & Shipley, WU (1983). Invasive bladder cancer: tumor configuration, lymphatic invasion and survival. J Urol 130: 895–902.
  14. Heney, NM, Ahmed, S & Flanagan, MJ (1983). Superficial bladder cancer. Progression and recurrence. J Urol 130: 1083–1086. | PubMed | ISI | ChemPort |
  15. Herr, HW (1997). Natural history of superficial bladder cancer: 10- to 20-year follow-up of treated patients. World J Urol 15: 84–88. | Article | PubMed | ISI | ChemPort |
  16. ISCN (1995). An International System for Human Cytogenetic Nomenclature. Mitelman F (ed.). S Karger: Basel
  17. Kakizoe, T, Fujita, J, Murase, T, Matsumotoko, K & Kishi, K (1980). Transitional cell carcinoma of the bladder in patients with renal pelvis and ureteral cancer. J Urol 124: 17–19. | PubMed | ISI | ChemPort |
  18. Kenworthy, P, Tanguay, S & Dinney, CP (1996). The risk of upper tract recurrence following cystectomy in patients with transitional cell carcinoma involving the distal ureter. J Urol 155: 501–504.
  19. Kiemeney, LA, Witjes, JA, Heijbroek, RP, Koper, NP, Verbeek, AL & Debruyne, FM (1993). Predictability of recurrent and progressive disease in individual patients with primary superficial bladder cancer. J Urol 150: 60–64. | PubMed |
  20. Lynch, CF & Cohen, MB (1995). Urinary system. Cancer 75: 316–345. | Article | PubMed | ChemPort |
  21. Miller, C, Mohandas, T, Wolf, D, Prokocimer, M, Rotter, V & Koeffler, HP (1986). Human TP53 gene localized to short arm of chromosome 17. Nature 319: 783–784. | Article | PubMed | ChemPort |
  22. Miyao, N, Tsai, YC, Lerner, SP, Olumi, AF, Spruk, CH, Gonzalez-Zulueta, M, Nichols, PW, Skinner, DG & Jones, PA (1993). Role of chromosome 9 in human bladder cancer. Cancer Res 53: 4066–4070. | PubMed | ISI | ChemPort |
  23. Morton, RA, Ewing, CM, Watkins, JJ & Isaac, WB (1995). The E-cadherin cell adhesion pathway in urologic malignancies. World J Urol 13: 364–372. | Article | PubMed |
  24. Nicol, D (1995). BCG in bladder cancer: a warning. Aust NZ J Med 25: 275–282.
  25. Parker, SL, Tong, T, Bolden, S & Wingo, PA (1996). Cancer statistics. Ca Cancer J Clin 46: 5–27. | PubMed | ISI | ChemPort |
  26. Prout, GR, BartonGriffin, PP & Friedell, GH (1992). Treated history of noninvasive grade 1 transitional cell carcinoma. The National Bladder Group. J Urol 148: 1413–1419. | PubMed | ISI |
  27. Reznikoff, CA, Belair, CD, Yeager, TR, Savelieva, E, Blelloch, RH, Puthenveettil, JA & Cuthill, SA (1996). Molecular genetic model of human bladder cancer pathogenesis. Semin Oncol 23: 571–584. | PubMed | ISI | ChemPort |
  28. Richie, JP, Shipley, WU & Yagoda, A (1989). Cancer of the bladder. In: Cancer Principles and Practice of Oncology, De Vita VT, Helman S and Rosenberg SA (eds), pp. 1008–1022. JB Lippincctt: Philadelphia
  29. Rosin, MP, Anwar, WA & Ward, AJ (1994). Inflammation, chromosomal instability, and cancer: the schistosomiasis model. Cancer Res 54: 1929–1933.
  30. Schmitz-Dräger, BJ, Jankevicius, F & Ackermann, R (1996). Molecular biology of dissemination in bladder cancer laboratory findings and clinical significance. World J Urol 14: 190–196.
  31. Sidransky, D, Frost, P, Von-Eschenbach, A, Oyasu, R, Preisinger, AC & Vogelstein, B (1992). Clonal origin of bladder cancer. N Eng J Med 326: 737–740.
  32. Thompson, RA, Campbell, EW, Kramer, HC, Jacobs, SC & Naslund, MJ (1993). Late invasive recurrence despite long-term survival for superficial bladder cancer. J Urol 149: 1010–1011.
  33. Union International Contre le Cancer (1978). TNM Classification of Malignant Tumors. Union International Contre le Cancer: Geneva
  34. Unyime, ON & Donald, LL (1994). Therapy of superficial cancer. Curr Opin Urol 4: 275–280.
  35. Williamson, MP, Elder, PA, Shaw, ME, Devlin, J & Knowles, MA (1995). P16 (CDKN2) is a major deletion target at 9p21 in bladder cancer. Hum Mol Genet 4: 1569–1577. | PubMed | ISI | ChemPort |
  36. Wolf, H & Hojgaard, K (1982). Urothelial dysplasia concomitant with bladder tumors as a determinant factor for future new occurrences. Lancet 2: 134–140.
  37. World Health Organization (1973). Histological Typing of Urinary Bladder Tumors. International Histological Classification of Tumors: Geneva
  38. Xu, X, Stower, MJ, Reid, NI & Garner, RC (1996). Burns PA Molecular screening of multifocal transitional cell carcinomas of the bladder using TP53 mutations as biomarkers. Clin Cancer Res 2: 1795–1800. | PubMed | ISI |
  39. Yao, A & Rubin, HA (1994). Critical test of the role of population density in producing transformation. Proc Natl Acad Sci USA 91: 7712–7716.