Résumés
Résumé
Les carcinomes nasopharyngés interpellent cliniciens et biologistes dans de nombreuses disciplines dont l’épidémiologie, la génétique, la virologie et l’immunologie. Ces tumeurs ont une répartition géographique tout à fait surprenante, faible dans la plus grande partie du monde, leur incidence est élevée en Extrême-Orient et en Afrique du Nord. Elles sont associées de façon constante au virus d’Epstein-Barr et leur étude revêt donc une importance particulière à l’heure où le virus d’Epstein-Barr est incriminé dans d’autres affections malignes humaines (carcinomes gastriques, mammaires et thyroïdiens, par exemple). Favoriser les échanges entre la recherche clinique sur les carcinomes nasopharyngés au Sud et la recherche fondamentale au Nord, tel était l’objectif de l’Atelier Nord-Sud sur les carcinomes nasopharyngés qui s’est tenu à l’Institut Gustave Roussy début décembre 2003.
Summary
Nasopharyngeal carcinomas (NPC) challenge clinicians and biologists in various fields including epidemiology, genetics, virology and immunology. These tumours have a striking geographical distribution. They are constantly associated with the Epstein-Barr virus (EBV) and contain a massive lymphocytic infiltrate. Their study has major implications especially at this moment while a pathological role of EBV is suspected in several other human epithelial malignancies (for example gastric, mammary and thyroid carcinomas). The North-South Workshop on Nasopharyngeal Carcinoma was held at the Institut Gustave-Roussy in early December 2003. Its main goal was to support the exchanges between clinical research on NPC in the South and basic research in the North. With regard to epidemiology and genetics, the main information was the possible existence of several susceptibility genes (including two of them on the 4p and 5p chromosomes). In virology, participants have emphasized the selection of peculiar EBV variants within the malignant cells and the expression of novel oncogenic viral proteins : LMP2 and BARF1. Cellular gene alterations also contribute to NPC development, especially inactivation of tumor suppressor genes located on the 3p chromosome. Therapeutic research was not forgotten. Hope of higher rate of cure relies on improved ballistic processes in radiotherapy (IMRT) and on the development of targeted therapeutics : induction of the lytic/productive viral cycle, gene therapy with conditional replicative adenoviruses, antitumor vaccination directed against the viral protein LMP2.
Parties annexes
Références
- 1. Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol 2002 ; 12 : 421-9.
- 2. Jeannel D, Hubert A, de Vathaire F, et al. Diet, living conditions and nasopharyngeal carcinoma in Tunisia - a case-control study. Int J Cancer 1990 ; 46 : 421-5.
- 3. Laouamri S, Hamdi-Cherif M, Sekfali N, et al. Facteurs de risque alimentaires du carcinome du nasopharynx dans la région de Sétif (Algérie). Rev Epidemiol Sante Publique 2001 ; 49 : 145-56.
- 4. Feng BJ, Huang W, Shugart YY, et al. Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4. Nat Genet 2002 ; 31 : 395-9.
- 5. Mokni-Baizig N, Ayed K, Ayed FB, et al. Association between HLA-A/-B antigens and -DRB1 alleles and nasopharyngeal carcinoma in Tunisia. Oncology 2001 ; 61 : 55-8.
- 6. Dardari R, Khyatti M, Jouhadi H, et al. Study of human leukocyte antigen class I phenotypes in Moroccan patients with nasopharyngeal carcinoma. Int J Cancer 2001 ; 92 : 294-7.
- 7. Sitki-Green D, Covington M, Raab-Traub N. Compartmentalization and transmission of multiple Epstein-Barr virus strains in asymptomatic carriers. J Virol 2003 ; 77 : 1840-7.
- 8. Nicholls J, Hahn P, Kremmer E, et al. Detection of wild type and deleted latent membrane protein 1 (LMP1) of Epstein-Barr virus in clinical biopsy material. J Virol Methods 2004 ; 116 : 79-88.
- 9. Edwards RH, Sitki-Green D, Moore DT, Raab-Traub N. Potential selection of LMP1 variants in nasopharyngeal carcinoma. J Virol 2004 ; 78 : 868-81.
- 10. Thornburg NJ, Pathmanathan R, Raab-Traub N. Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma. Cancer Res 2003 ; 63 : 8293-301.
- 11. Murono S, Inoue H, Tanabe T, et al. Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells. Proc Natl Acad Sci USA 2001 ; 98 : 6905-10.
- 12. Nanbo A, Inoue K, Adachi-Takasawa K, Takada K. Epstein-Barr virus RNA confers resistance to interferon-alpha-induced apoptosis in Burkitt’s lymphoma. EMBO J 2002 ; 21 : 954-65.
- 13. Tsimbouri P, Drotar ME, Coy JL, Wilson JB. Bcl-xL and RAG genes are induced and the response to IL-2 enhanced in EmuEBNA-1 transgenic mouse lymphocytes. Oncogene 2002 ; 21 : 5182-7.
- 14. Khabir A, Ghorbel A, Daoud J, et al. Similar BCL-X but different BCL-2 levels in the two age groups of North African nasopharyngeal carcinomas. Cancer Detect Prev 2003 ; 27 : 250-5.
- 15. Decaussin G, Sbih-Lammali F, de Turenne-Tessier M, et al. Expression of BARF1 gene encoded by Epstein-Barr virus in nasopharyngeal carcinoma biopsies. Cancer Res 2000 ; 60 : 5584-8.
- 16. Gulley ML, Nicholls JM, Schneider BG, et al. Nasopharyngeal carcinomas frequently lack the p16/MTS1 tumor suppressor protein but consistently express the retinoblastoma gene product. Am J Pathol 1998 ; 152 : 865-9.
- 17. Ablashi D, Bornkamm GW, Boshoff C, et al. Proceedings of the IARC Working Group on the evaluation of carcinogenic risks to humans. Epstein-Barr virus and Kaposi’s sarcoma herpesvirus/human herpesvirus 8. Lyon, France, 17-24 June 1997. IARC Monogr Eval Carcinog Risks Hum 1997 ; 70 : 1-492.
- 18. Dardari R, Hinderer W, Lang D, et al. Antibody responses to recombinant Epstein-Barr virus antigens in nasopharyngeal carcinoma patients : complementary test of ZEBRA protein and early antigens p54 and p138. J Clin Microbiol 2001, 39 : 3164-70.
- 19. Chan KCA, Lo YMD. Circulating EBV DNA as a tumor marker for nasopharyngeal carcinoma. Semin Cancer Biol 2002 ; 12 : 489-96.
- 20. Liu HX, Ding YQ, Li X, Yao KT. Investigation of Epstein-Barr virus in Chinese colorectal tumors. World J Gastroenterol 2003 ; 9 : 2464-8.
- 21. Shimakage M, Kawahara K, Sasagawa T, et al. Expression of Epstein-Barr virus in thyroid carcinoma correlates with tumor progression. Hum Pathol 2003 ; 34 : 1170-7.
- 22. Zur Hausen A, Brink AA, Craanen ME, et al. Unique transcription pattern of Epstein-Barr virus (EBV) in EBV-carrying gastric adenocarcinomas : expression of the transforming BARF1 gene. Cancer Res 2000 ; 60 : 2745-8.
- 23. Huang J, Chen H, Hutt-Fletcher L, et al. Lytic viral replication as a contributor to the detection of Epstein-Barr virus in breast cancer. J Virol 2003 ; 77 : 13267-74.
- 24. Feng WH, Israel B, Raab-Traub N, et al. Chemotherapy induces lytic EBV replication and confers ganciclovir susceptibility to EBV-positive epithelial cell tumors. Cancer Res 2002 ; 62 : 1920-6.
- 25. Li JH, Shi W, Chia M, et al. Efficacy of targeted FasL in nasopharyngeal carcinoma. Mol Ther 2003 ; 8 : 964-73.
- 26. Ferlay J, Bray F, Pisani P, Parkin DM. IARC cancerBase n° 5. Lyon : IARC Press, 2001.