Skip to main content
SpringerLink
Log in

Histopathologische und molekulare Prognosefaktoren des Zervixkarzinoms

Histopathologic and molecular prognostic factors for cervical carcinoma

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Die weltweite Inzidenz des Zervixkarzinoms gilt für alle histologischen Typen des invasiven Zervixkarzinoms. In Populationen mit sinkender Inzidenz steigt der Anteil von Adenokarzinomen. In Deutschland stellt das Zervixkarzinom bei 25–35-jährigen Frauen fast 20% aller Malignome, bei Frauen über 65 Jahre jedoch nur 3%. Der kausale Zusammenhang zwischen HPV-Infektion und der Entstehung eines Zervixkarzinoms gilt heute als gesichert. Jedoch führt nicht jede Infektion mit hoch onkogenen HPV-Typen auch zum Zervixkarzinom, sodass neben der viralen Infektion weitere zelluläre, immunologische und genetische Mechanismen eine wichtige Rolle spielen. Obwohl zentrale Regulationsmechanismen der HPV-vermittelten Kanzerogenese detailliert untersucht wurden und bereits neue innovative Strategien zur präventiven und therapeutischen Vakzinierung klinisch geprüft werden, sind molekulare Prognosefaktoren in der klinischen Praxis ohne Bedeutung. Die Prognose wird im Wesentlichen von der Tumorausdehnung und histopathologischen Faktoren bestimmt.

Abstract

In Germany, cervical cancers comprise about 20% of all malignant tumors among 25–35-year-old women, but only 3% among women older than 65 years. A relative increase of adenocarcinomas has been observed in populations with a decreasing incidence of cervical cancers. It is well accepted that specific types of human papillomaviruses (HPV) are the principal etiologic agents for cervical cancer. In addition to viral infection, mutational genetic events and immunological factors play a critical role in the multistep process of cancerogenesis. Although HPV-induced neoplastic transformation has been well examined and vaccination strategies are in clinical development, clinically relevant molecular prognostic markers have not yet been identified. To date, the most important prognostic factors of cervical cancer are tumor stage and histopathologic characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6

Literatur

  1. Benedet JL, Odricino F, Maisonneuve P et al. (2001) Carcinoma of the cervix uteri. In: FIGO Annual report on the results of treatment in gynaecological cancer. 24th vol. J Epidemiol Biostat 6: 7–44

    PubMed  Google Scholar 

  2. Burghardt E (1993) Cervical cancer: Criteria of spread. In: Burghardt E, Webb MJ, Monaghan JM, Kindermann G (eds) Surgical gynecologic oncology. Thieme, Stuttgart New York

  3. Duarte-Franco E, Franco EL (2001) Determinants of patient survival in cervical cancer: an overview. CME J Gynecol Oncol 6: 173–183

    Google Scholar 

  4. Duffy MJ, Duggan C (2004) The urokinase plasminogen activator system: a rich source of tumour markers for the individualised management of patients with cancer. Clin Biochem 37: 541–548

    Article  PubMed  Google Scholar 

  5. Gombos Z, Xu X, Chu CS et al. (2005) Peritumoral lymphatic vessel density and vascular endothelial growth factor C expression in early-stage squamous cell carcinoma of the uterine cervix. Clin Cancer Res 11: 8364–8371

    Article  PubMed  Google Scholar 

  6. Hacker NF, Wain GV, Nicklin JL (1995) Resection of bulky positive lymph nodes in patients with cervical carcinoma. Int J Gynecol Cancer 5: 250–256

    Article  PubMed  Google Scholar 

  7. Hazelbag S, Kenter GG, Gorter A et al. (2004) Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancer. Int J Cancer 112: 1020–1028

    Article  PubMed  Google Scholar 

  8. Heck DV, Yee CL, Howley PM et al. (1992) Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomaviruses. Proc Natl Acad Sci USA 89: 4442–4446

    Article  PubMed  Google Scholar 

  9. Hernadi Z, Szarka K, Sapy T et al. (2003) The prognostic significance of HPV-16 genome status of the lymph nodes, the integration status and p53 genotype in HPV-16 positive cervical cancer: a long term follow up. BJOG 110: 205–209

    PubMed  Google Scholar 

  10. Horn LC, Fischer U, Bilek K (2001) Pathologisch-anatomische Aufarbeitung und morphologische Basisinformationen für das Management von Dysplasien und Karzinomen der Cervix uteri. Zbl Gynäk 123: 255–265

    Google Scholar 

  11. Jee SH, Won SY, Yun JE et al. (2004) Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis. Int J Gynaecol Obstet 85: 301–308

    Article  PubMed  Google Scholar 

  12. Kanda K, Ueda M, Futakuchi H et al. (2005) Transcriptional expression of the genes implicated in angiogenesis and tumor invasion in cervical carcinomas. Gynecol Oncol 98: 453–461

    Article  PubMed  Google Scholar 

  13. Klaes R, Woerner SM, Ridder R et al. (1999) Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes. Cancer Res 59: 6132–6136

    PubMed  Google Scholar 

  14. Kurman RJ, Norris HJ, Wilkinson E (1992) Tumors of the cervix, vagina, and vulva. Atlas of tumor pathology, 3rd series, fasc. 4.AFIP, Washington DC

  15. Lindel K, de Villiers EM, Burri P et al. (2006) Impact of viral E2-gene status on outcome after radiotherapy for patients with human papillomavirus 16-positive cancer of the uterine cervix. Int J Radiat Oncol Biol Phys 65: 760–765

    Article  PubMed  Google Scholar 

  16. Löning Th, Riethdorf L (2001) Pathologie der weiblichen Genitalorgane III. Pathologie des Uterus, der Vagina und Vulva. Springer, Berlin Heidelberg New York

  17. Muller H, Lukas J, Schneider A et al. (1994) Cyclin D1 expression is regulated by the retinoblastoma protein. Proc Natl Acad Sci USA 91(8): 2945–2949

    Article  PubMed  Google Scholar 

  18. Munger K, Basile JR, Duensing S et al. (2001) Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene 20: 7888–7898

    Article  PubMed  Google Scholar 

  19. Ohno T, Nakayama Y, Nakamoto S et al. (2003) Measurement of serum squamous cell carcinoma antigen levels as a predictor of radiation response in patients with carcinoma of the uterine cervix. Cancer 97: 3114–3120

    Article  PubMed  Google Scholar 

  20. Padera TP, Kadambi A, di Tomaso E et al. (2002). Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 296: 1883–1886

    Article  PubMed  Google Scholar 

  21. Pitson G, Fyles A (2001) Uterine cervix cancer. In: UICC (Gospodarowicz MK, Henson DE, Hutter RVP, O’Sullivan B, Sobin LH, Wittekind Ch, eds) Prognostic factors in cancer, 2nd en. Wiley & Sons, New York, pp 501–513

  22. Platz CE, Benda JA (1995) Female genital tract cancer. Cancer 75: 270–294

    Article  PubMed  Google Scholar 

  23. Riethdorf L, Ramirez-Ponas J, Kühler-Obbarius C (1999) Diagnostik und Therapie zervikaler Plattenepitheldysplasien. Pathologe 20: 34–41

    Article  PubMed  Google Scholar 

  24. Riethdorf L, Riethdorf S, Petersen S et al. (1999) Urokinase gene expression indicates early invasive growth in squamous cell lesions of the uterine cervix. J Pathol 189: 245–250

    Article  PubMed  Google Scholar 

  25. Rosty C, Sheffer M, Tsafrir D et al. (2005) Identification of a proliferation gene cluster associated with HPV E6/E7 expression level and viral DNA load in invasive cervical carcinoma. Oncogene 24(47): 7094–7104

    Article  PubMed  Google Scholar 

  26. Tavassoli FA, Devilee P (eds) (2003) Pathology and genetics of tumours of the breast and female genital organs. WHO Classification of Tumours. IARC Press, Lyon

  27. Van Trappen PO, Ryan A, Carroll M et al. (2002) A model for co-expression pattern analysis of genes implicated in angiogenesis and tumour cell invasion in cervical cancer. Br J Cancer 87: 537–544

    Article  PubMed  Google Scholar 

  28. Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81: 323–330

    Article  PubMed  Google Scholar 

  29. Wentzensen N, Vinokurova S, von Knebel Doeberitz M (2004) Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res 64: 3878–3884

    Article  PubMed  Google Scholar 

  30. Wilke CM, Hall BK, Hoge A et al. (1996) FRA3B extends over a broad region and contains a spontaneous HPV16 integration site: direct evidence for the coincidence of viral integration sites and fragile sites. Hum Mol Genet 5: 187–195

    Article  PubMed  Google Scholar 

  31. Wright TC, Ferenczy A, Kurman JR (1994) Carcinoma and other tumors of the cervix. In: Kurman RJ (ed) Blaustein’s pathology of the female genital tract. Springer, Berlin Heidelberg New York

Download references

Danksagung

Die Autoren danken Prof. Dr. H. P. Sinn, Institut f. Pathologie der Universität Heidelberg für seine großzügige Unterstützung.

Interessenkonflikt

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Author information

Authors and Affiliations

  1. Universitätsfrauenklinik Bonn

    T. W. Park

  2. Universitätsfrauenklinik Hamburg

    K. Behrens

  3. Referenzzentrum für Gynäkopathologie und -Zytologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg

    T. Löning

Authors
  1. T. W. Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Behrens
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Löning
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Löning.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, T.W., Behrens, K. & Löning, T. Histopathologische und molekulare Prognosefaktoren des Zervixkarzinoms. Onkologe 12, 869–878 (2006). https://doi.org/10.1007/s00761-006-1107-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00761-006-1107-6

Schlüsselwörter

Keywords

Search

Navigation