Download PDF
Aktuelle Urol 2002; 33(3): 201-205
DOI: 10.1055/s-2002-32116
Klinische Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Humane Papillomaviren in Harnblasenkarzinomen: Epiphänomen oder Subentität?

Human Papillomavirus in Bladder Cancer: Epiphenomenon or Subentity?V.  Rohde1 , H.  Ballo2 , H.  Schmelz1 , T.  Nicolla3 , A.  Hörlin2 , J.  Miller1 , W.  Weidner1 , T.  Kahn3
  • 1Klinik und Poliklinik für Urologie und Kinderurologie, Universitätskliniken Gießen
  • 2Institut für Pathologie, Universität Frankfurt
  • 3Deutsches Krebsforschungszentrum Heidelberg
Further Information

Publication History

Publication Date:
07 June 2002 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Fragestellung: Die humanen Papillomaviren 16 und 18 sind die am häufigsten nachgewiesenen Genotypen in genitalen Malignomen. Eine strenge Assoziation zwischen dem Nachweis von HPV 16 und 18 und dem Auftreten von Zervixkarzinomen ist bekannt, eine mögliche Assoziation beim Karzinom der Harnblase hingegen wird kontrovers diskutiert. Die geringe Inzidenz der HPV Typen 6 und 11 und die geringe Progression HPV 6 und 11positiver, benigner Tumoren hat dazugeführt, diese als „low risk virus” zu klassifizieren. In der vorliegenden Studie wurde die Prävalenz von HPV 16, 18 sowie von 6 und 11analysiert. Material und Methode: Um die Inzidenz der HPV Typen 6,11 und 16 und 18 in histologischen Schnittpräparaten zu bestimmen, wurden 48 formalin-fixierte und Paraffin-eingebettete Harnblasenkarzinome unterschiedlichen Stagings und Gradings auf das Vorhandensein von HPV DNA 6,11 sowie von 16 und 18 mit der Polymerasekettenreaktion untersucht. Ergebnisse: Interessanterweise konnte in 4 Harnblasenkarzinomen und in 4 nicht neoplastischen Harnblasengeweben HPV 6/11 nachgewiesen werden. Ein Nachweis von HPV 16 oder 18 konnte dagegen nicht erbracht werden. Schlussfolgerung: Zusammenfassend scheinen HPV 16 und 18 bei der untersuchten Patientengruppe keine Rolle in der Entstehung des Harnblasenkarzinoms zu spielen. Der Nachweis von HPV6/11-Infektionen zeigt allerdings, dass das Blasenepithel von Papillomaviren infiziert werden kann. Die Bedeutung der nachgewiesenen HPV 6/11 in einem Mehrschrittmechanismus einer Karzinomentstehung zur möglichen Abgrenzung einer Subentität muss in weiteren Studien abgeklärt werden.

Abstract

Purpose: Human papillomavirus types 16 and 18 are the most frequent genotypes identified in genital malignancies. A strong association between the detection of human papillomavirus (HPV) and cervical Cancer is known to exist, but there is substantial controversy regarding the association of HPV and cancers of the bladder.The low incidence of HPV 6 and 11 in carcinomas and the rare progression of benign, HPV 6 and 11 positive tumors has led to the classification of low risk virus. In the present study the prevalence of the HPV 16,18 and 6 and 11 was analyzed in human bladder cancer. Material and Methods: To determinate the incidence of HPV 6,11 and 16 and 18 in histological section of human bladder cancer, 48 formalin fixed and paraffin embedded bladder tumor specimens with different staging and grading were analyzed for the presence of HPV DNA using the polymerase chain reaction (PCR). These results were confirmed by southern blot hybridization using radiolabbeled probes for HPV DNA types 6/11 and 16 and 18. Results: Interestinctly four carcinoms of the bladder and four non neoplastic bladder tissue specimens were positive for HPV 6/11. No HPV 16 and 18 DNA was detected in any specimens. Conclusions: We conclude that these HPV 16 and 18 seem not to have a significant role in the development of bladder cancer in the analysed population. However, the detection of HPV6/11 infections show, that the bladder epithelium can be infected by HPVs. Therefore the relevance of these HPV 6/11 in the multistep process of bladder carcinogenesis should be examined in further studies.

Schlüsselwörter

Humane Papillomaviren - Harnblasenkarzinom - Polymerasekettenreaktion

Key words

Papillomavirus, human - Bladder cancer - Polymerase chain reaction

Literatur

  • 1 Anwar K, Phil M, Naiki H, Nakakuki K, Inuzuka M. High frequency of human papillomavirus infection in carcinoma of the urinary bladder.  Cancer. 1992;  70 1969-1973
    PubMedGoogle Scholar
  • 2 Boucher N R, Scholefield J H, Anderson J B. The aetiological significance of human papillomavirus in Bladder cancer.  Br J Urol. 1996;  78 866-869
    PubMedGoogle Scholar
  • 3 Bryant P, Davies P, Wilson D. Detection of human papillomavirus DNA in cancer of urinary bladder by in situ hybridisation.  Br J Urol. 1991;  68 49-52
    PubMedGoogle Scholar
  • 4 Bryant P, Skelly J, Wilson D. Demonstration of papillomavirus structural antigen in human urinary bladder neoplasia.  Br J Urol. 1987;  60 405-409
    PubMedGoogle Scholar
  • 5 Chang F, Lipponen P, Tervahauta A, Syrjänen S, Syrjänen K. Transitional cell carcinoma of the bladder: Failure to demonstrate human papillomavirus deoxyribonucleic acid by in situ hybridization and polymerase chain reaction.  J Urol. 1994;  152 1429-1433
    PubMedGoogle Scholar
  • 6 Chetsanga C, Malström P U, Gyllensten U, Moreno-Lopez J, Dinter Z, Pettersson U. Low incidence of human papillomavirus type 16 in bladder tumor detected by the polymerase chain reaction.  Cancer. 1991;  69 1208-1211
    PubMedGoogle Scholar
  • 7 Dallas P B, Flanagan L, Nightingale B N, Morris B J. Polymerase chain reaction for fast, nonradioactive detection of high- and low risk papilloma virus types in routine cervical specimens and in biopsies.  J Med Virol. 1989;  27 105-111
    PubMedGoogle Scholar
  • 8 Grassmann K, Wilczynski S P, Cook N, Rapp B, Iftner T. HPV 6 variants from malignant tumors with sequence alterations in the regulatory region do not reveal differances in the activities of the oncogene promoters but do contain amino acid exchanges in the E6 and E7 proteins.  Virology. 1996;  223 185-197
    CrossrefPubMedGoogle Scholar
  • 9 Howley P M. Viral oncogenesis. In: Mendellsohn J, Howley PM, Liotta LA. The molekular basis of cancer WB Saunders company 1995: 38-58
    Google Scholar
  • 10 Iwaswa A, Kumamoto Y, Maruta H, Fukushima M, Fujinaga K, Kodama N. Presence of human papillomavirus 6/11 DNA in condylomata acuminata of the urinary bladder.  Urol Int. 1992;  48 235-238
    PubMedGoogle Scholar
  • 11 Karlsen F, Kalantari M, Chitemerere M, Johansson B, Hagmar B. Modifications of human and viral deoxyribonucleic acid by formaldehyde fixation.  Lab Invest. 1994;  71 604-612
    PubMedGoogle Scholar
  • 12 Knowles M A. Human papillomavirus sequences are not detectable by southern blotting or general primer mediated polymerase chain reaction in transitional tumours of the bladder.  Urol Res. 1992;  20 297-301
    CrossrefPubMedGoogle Scholar
  • 13 Kondoh G, Li Q, Pan H, Hakura A. Transgenic models for papilloma associated multistep carcinogenesis.  Intervirology. 1995;  38 181-186
    PubMedGoogle Scholar
  • 14 La Rue H, Simoneau M, Fradet Y. Human papillomavirus in transitional cell carcinoma of the urinary bladder.  Clin Cancer Res. 1995;  1 435-440
    PubMedGoogle Scholar
  • 15 Lopez-Beltran A, Escudero A L, Vicioso L, Munoz E, Carrasco J C. Human papillomavirus DNA as a factor determining the survival of bladder cancer patients.  Br J Urol. 1996;  73 124-127
    PubMedGoogle Scholar
  • 16 Ludwig M, Kochel H G, Fischer C, Ringert R H, Weidner W. Human papillomavirus in tissue of bladder and bladder carcinoma specimens. A primilinary study.  Eur Urol. 1996;  30(1) 96-102
    PubMedGoogle Scholar
  • 17 Maloney K, Wiener J S, Walther P J. Oncogenic human papillomavirus are rarely associated with squamous cell carcinoma of the bladder: evaluation by differential polymerase chain reaction.  J Urol. 1994;  154 360-364
    PubMedGoogle Scholar
  • 18 Matusukura T, Koi S, Sugase M. Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers.  Virology. 1989;  172 63-72
    CrossrefPubMedGoogle Scholar
  • 19 Mevorach R A, Cos L R, Di Sant'Agnese P A, Stoler M. Human papillomavirus type 6 in grade 1 transitional cell carcinoma of the Urethra.  J Urol. 1990;  143 126-128
    PubMedGoogle Scholar
  • 20 Micali G, Innocenzi D, Nasca M R, Musumeci M L, Ferru F, Greco M. Squamous cell carcinoma of the penis.  J Am Acad Dermatol. 1996;  35 432-451
    CrossrefPubMedGoogle Scholar
  • 21 Mvula M, Iwasaka T, Iguchi A, Nakamura S, Masaki Z, Sigimori H Do. Human papillomavirus have a role in the pathogenesis of bladder carcinoma?.  J Urol. 1996;  155 471-474
    PubMedGoogle Scholar
  • 22 Neubauer A, Neubauer B, He M, Effert P, Iglehart D, Roy A, Frye A, Liu E. Analysis of gene amplification in archival tissue by differential polymerase chain reaction.  Oncogene. 1992;  7 1019-1025
    PubMedGoogle Scholar
  • 23 Oft M, Bohm S, Wilczynski S P, Iftner T. Expression of the different viral mRNAs of human papilloma virus 6 in a squamous cell carcinoma of the bladder and the cervix.  Int J Cancer. 1993;  53 924-931
    PubMedGoogle Scholar
  • 24 Querci Della Rovere G, Oliver R T, McCance D J, Castro J E. Development of the bladder tumour HPV type 11 DNA after renal transplantation.  Br J Urol. 1988;  62 36-38
    PubMedGoogle Scholar
  • 25 Rapp B, Pawellek A, Kraetzer F, Schaefer M, May C, Purdie K, Grassmann K, Iftner T. Cell-type-specific separate regulation of the E6 and E7 promoters of human papillomavirus type 6a by the viral transcription factor E2.  J Virol. 1997;  71(9) 6956-6966
    PubMedGoogle Scholar
  • 26 Rotola A, Monini P, Di Luca D, Savioli A, Simone S, Secchiero P, Reggiani A, Cassai E. Presence and physical state of HPV DNA in prostate and urinary-tract tissues.  Int J Cancer. 1992;  52 359-365
    PubMedGoogle Scholar
  • 27 Sano T, Sakurai S, Fukuda T, Nakajima T. Unsuccessful effort to detect human papillomavirus DNA in urinary bladder cancers by the polymerase chain reaction and in situ hybridisation.  Pathol Int. 1995;  45 506-512
    PubMedGoogle Scholar
  • 28 Sambrook J, Frisch E, Maniatis T. Molecular clonig. A laboratory manual. Cold Spring Harbor: Laboratory press: Second edition 1986
    Google Scholar
  • 29 Scheffner M, Munger K, Byrne J C, Howley P M. State of the p53 and retinoblastom genes in Proc human cervical carcinoma cell lines.  Natl Acad Sci USA. 1991;  88 5523-5527
    CrossrefPubMedGoogle Scholar
  • 30 Shibutani F, Schoenberg M, Carpiniello V, Malloy T R. Human papillomavirus associated with bladder cancer.  Urology. 1992;  40 15-17
    CrossrefPubMedGoogle Scholar
  • 31 Spiessl B, Beahrs O H, Hermanek P, Hutter R VP, Scheibe O, Sobin L H, Wagner G. UICC TNM 31 Atlas. Illustrated guide to the TNM/pTNM classification of malignant tumours. Ed.3., 3nd revision. Berlin: Springer-Verlag 1997
    Google Scholar
  • 32 Steinbeck G, Plato N, Norell S. Urothelial cancer and some industry related chemicals: An evaluation of the epidemiologic literature.  Am J Ind Med. 1992;  17 371-378
    PubMedGoogle Scholar
  • 33 Schlehofer J. The tumor suppressive properties of adeno-associated viruses.  Mutat Res. 1994;  305(3) 303-313
    PubMedGoogle Scholar
  • 34 Sur M, Cooper K, Allard U. Investigation of human papillomavirus in transitional cell carcinomas of the urinary bladder in South Africa.  Pathology. 2001;  33(1) 17-20
    PubMedGoogle Scholar
  • 35 Turazza E, Lapena A, Sprovieri O, Torre C P, Gurucharri C, Maciel A, Lema B, Grinstein S, Kahn T. Low risk human papillomavirus types 6 and 11 associated with carcinomas of the genital and upper aero-digestive tract.  Acta Obstet Gynecol Scand. 1997;  76 271-276
    PubMedGoogle Scholar
  • 36 Zur Hausen H. Human papillomavirus in the pathogenesis of anogenital cancer.  Virology. 1991;  84 9-13
    PubMedGoogle Scholar

Dr. med. V. Rohde

Klinik und Poliklinik für Urologie und Kinderurologie der Universitätskliniken Gießen

Rudolf-Buchheim-Str. 7

35392 Gießen

Phone: 0641-9944508

Fax: 06841-9944509

      >