DOI QR코드

DOI QR Code

Expression of Epstein Barr Virus Encoded EBNA1 and LMP1 Oncoproteins in Nasopharyngeal Carcinomas from Northeast India

  • Borthakur, Parikhit (Department of Bioengineering and Technology, GU IST, Gauhati University) ;
  • Kataki, Kangkana (Department of Bioengineering and Technology, GU IST, Gauhati University) ;
  • Keppen, Chenole (Healthcare Laboratory and Research Centre, Naga Hospital Authority) ;
  • Khamo, V. (Healthcare Laboratory and Research Centre, Naga Hospital Authority) ;
  • Medhi, Subhash (Department of Bioengineering and Technology, GU IST, Gauhati University) ;
  • Deka, Manab (Department of Bioengineering and Technology, GU IST, Gauhati University)
  • Published : 2016.07.01

Abstract

Background: Nasopharyngeal carcinoma (NPC), a malignancy arising from the epithelial lining of the nasopharynx, is distinct from others cancers in terms of its epidemiologic features. It is rare in most parts of the world except for a few regions with populations of Mongoloid origin. Objectives: To study the expression pattern of Epstein Barr virus (EBV) encoded oncoproteins EBNA1 and LMP1 in different histological types of NPC and to correlate expression patterns with sex, age and histological types. Materials and Methods: A total of 40 formalin-fixed, paraffin-embedded NPC biopsy samples and tissues from 20 healthy controls were collected to study the expression level of EBNA1 and LMP1 using immunohistochemistry. Results: EBNA1 and LMP1 expression was found in 92.5% and 90% respectively, of the cases and none of the control specimens. The expression patterns of EBNA1 and LMP1 were determined to be statistically significant (p<0.05) when correlated with sex, age and histological distributions. Also immunohistochemistry was found to be a sensitive technique in the detection of EBV. Conclusions: The study reveals that the potent oncoproteins EBNA1 and LMP1 were over expressed in our population cohort. Our findings are to some extent inconsistent with earlier reports as our population showed a higher expression of both EBNA1 and LMP1 compared to other studies.

Keywords

References

  1. Armstrong RW, Imrey PB, Lye MS, et al (1998). Nasopharyngeal carcinoma in Malaysian Chinese: salted fish and other dietary exposures. Int J Cancer, 77, 228-35. https://doi.org/10.1002/(SICI)1097-0215(19980717)77:2<228::AID-IJC11>3.0.CO;2-7
  2. Babcock GJ, Decker LL, Volk M, et al (1998). EBV persistence in memory B cells in vivo. Immunity, 9, 395-04. https://doi.org/10.1016/S1074-7613(00)80622-6
  3. Barnes EL, Eveson JW, Reichart P, et al (2005). Pathology and genetics of head and neck tumours. World Health Organization Classification of Tumours. Lyon, France: IARC Press.
  4. Busson P, Keryer C, Ooka T, et al (2002). EBV-associated nasopharyngeal carcinomas: from epidemiology to virustargeting strategies. Trends Microbiol, 12, 356-60.
  5. Chan AT, Teo PM, Johnson PJ (2002). Nasopharyngeal carcinoma. Ann Oncol, 13, 1007-15. https://doi.org/10.1093/annonc/mdf179
  6. Chang ET, Adami HO (2006). The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev, 15, 1765-77. https://doi.org/10.1158/1055-9965.EPI-06-0353
  7. Edefonti V, Nicolussi F, Polesel J, et al (2015). Nutrient-based dietary patterns and nasopharyngeal cancer: evidence from an exploratory factor analysis. Br J Cancer, 112, 446-54. https://doi.org/10.1038/bjc.2014.611
  8. Farrow DC, Vaughan TL, Berwick M, et al (1998). Diet and nasopharyngeal cancer in a low risk population. Int J Cancer, 78, 675-79. https://doi.org/10.1002/(SICI)1097-0215(19981209)78:6<675::AID-IJC2>3.0.CO;2-J
  9. Feng BJ, Huang W, Shugart YY, et al (2002). Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4. Nat Genet, 31, 395-99. https://doi.org/10.1038/ng932
  10. Guo Q, Tham IWK, Lin S, et al (2012). Prognostic significance of pre-treatment latent membrane protein 1 from nasopharyngeal swabs for stage III-IVA nasopharyngeal carcinoma. Head Neck Oncol, 4, 81.
  11. Henle W, Henle G, Ho HC, et al (1970). Antibodies to Epstein-Barr virus in nasopharyngeal carcinoma, other head and neck neoplasms and control groups. J Natl Cancer Inst, 44, 225-31.
  12. Ibrahim B, Yousif E, Yousif MY, et al (2015). Immunohistochemical expression of Latent membrane protein-1 (LMP-1) among Sudanese patients with Nasopharyngeal carcinoma. Int J Res - Granthaalayah, 3, 101-07.
  13. Kataki AC, Simons MJ, Das AK, et al (2011). Nasopharyngeal carcinoma in the Northeastern states of India. Chin J Cancer, 30, 106-13. https://doi.org/10.5732/cjc.010.10607
  14. Khaled MB (2014). Effect of Epstein-Barr virus infection on predisposition and postradiotherapeutic prognostic value among Libyan patients with nasopharyngeal cancer. Egyptian J Otolaryngol, 30, 201-07 https://doi.org/10.4103/1012-5574.138466
  15. Khan G, Miyashita EM, Yang B, et al (1996). Is EBV Persistence in Vivo a Model for B cell Homeostasis?. Immunity, 5, 173-79. https://doi.org/10.1016/S1074-7613(00)80493-8
  16. Korcum AF, Ozyar E, Ayhan A (2006). Epstein-Barr virus genes and nasopharyngeal cancer. Turk J Cancer, 36, 97-07.
  17. Kouvidou Ch, Kanavaros P, Papaioannou D et al (1995). Expression of bcl-2 and p53 proteins in nasopharyngeal carcinoma. Absence of correlation with the presence of EBV encoded EBERl-2 transcripts and latent membranemprotein-1. Clin Mol Pathol, 48, 17-22. https://doi.org/10.1136/mp.48.1.M17
  18. Liu MY, Shih YY, Li LY, et al (2000). Expression of the Epstein-Barr virus BHRF1 gene, a homologue of Bcl-2, in nasopharyngeal carcinoma tissue. J Med Virol, 61, 241-50 https://doi.org/10.1002/(SICI)1096-9071(200006)61:2<241::AID-JMV11>3.0.CO;2-2
  19. Mirabelli MC, Hoppin JA, Tolbert PE, et al (2000). Occupational exposure to chlorophenol and the risk of nasal and nasopharyngeal cancers among U.S. men aged 30 to 60. Am J Ind Med, 37, 532-41. https://doi.org/10.1002/(SICI)1097-0274(200005)37:5<532::AID-AJIM9>3.0.CO;2-A
  20. Moumad K, Lascorz J, Bevier M, et al (2013). Genetic polymorphisms in host innate immune sensor genes and the risk of nasopharyngeal carcinoma in North Africa. Genetics Immunity, 3, 971-77
  21. Muir CS (1971). Nasopharyngeal carcinoma in non-chinese populations with special reference to South East Asia and Africa. Brit J Cancer, 8, 351-63.
  22. Niedobitek G, Hansmann LM, Herbst H, et al (1991). Epstein-Barr virus and carcinoma; undifferentiated carcinoma but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus. J Pathol, 165, 17-24. https://doi.org/10.1002/path.1711650105
  23. Niedobitek G (2000). Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Mol Pathol, 53, 248-54. https://doi.org/10.1136/mp.53.5.248
  24. Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB, editors (2002). Cancer incidence in five continents, Vol. VIII. IARC Scientific Publications, No. 155, Lyon: IARC
  25. Robinson M, Suh YE, Paleri V, et al (2013). Oncogenic human papillomavirus-associated nasopharyngeal carcinoma: an observational study of correlation with ethnicity, histological subtype and outcome in a UK population. Infect Agent Cancer, 8, 30. https://doi.org/10.1186/1750-9378-8-30
  26. Razak AR, Siu LL, Liu FF, et al (2010). Nasopharyngeal carcinoma: the next challenges. Eur J Cancer, 46, 1967-78. https://doi.org/10.1016/j.ejca.2010.04.004
  27. Shao YM, Poirier S, Ohshima H, et al (1998). Epstein-Barr virus activation in Raji cells by extracts of preserved food from high risk areas for nasopharyngeal carcinoma. Carcinogenesis, 9, 1455-57.
  28. Simons MJ (2011). Nasopharyngeal carcinoma as a paradigm of cancer genetics. Chin J Cancer, 30, 79-84. https://doi.org/10.5732/cjc.010.10609
  29. Tabyaoui I, Serhier Z, Sahraoui S, et al (2013). Immunohistochemical expression of latent membrane protein 1(LMP1) and p53 in nasopharyngeal carcinoma: Moroccan experience. Afr Health Sci, 13, 710-17.
  30. Tsao SW, Tsang CM, To KF (2015). The role of Epstein-Barr virus in epithelial malignancies. J Pathol, 235, 323-33. https://doi.org/10.1002/path.4448
  31. Umar B, Ahmed R (2014). Nasopharyngeal carcinoma, an analysis of histological subtypes and their association with EBV, a study of 100 cases of Pakistani population. Asian J Med Sci, 5, 16-20.
  32. Vasef MA, Ferlito A, Weiss LM (1997). Nasopharyngeal carcinoma, with emphasis on its relationship to Epstein-Barr virus. Ann Otol Rhinol Laryngol, 106, 348-56. https://doi.org/10.1177/000348949710600416
  33. Vaughan TL, Stewart PA, Teschke K, et al (2000). Occupational exposure to formaldehyde and wood dust and nasopharyngeal cancer. Occup Environ Med, 57, 376-84. https://doi.org/10.1136/oem.57.6.376
  34. Vera-Sempere FJ, Burgos JS, Botella MS, et al (1996). Immunohistochemical expression of Epstein- Barr virusencoded membrane protein (LMP1) in paraffin sections of EBV-associated nasopharyngeal carcinoma in Spanish patients. Oral Oncol, Eur J Cancer B, 32, 163-68.
  35. Wolf H, Hausen HZ, Becker Y (1973). Epstein-Barr viral genomes in epithelial nasopharyngeal carcinoma cells. Nature New Biol, 244, 245-47.
  36. Xiao L, Z-y H, Dong X, et al (2014). Targeting epstein-barr virus oncoprotein LMP1-mediated glycolysis sensitizes nasopharyngeal carcinoma to radiation therapy. Oncogene. 33, 4568-78 https://doi.org/10.1038/onc.2014.32
  37. Xiong W, Zeng ZY, Xia JH, et al (2004). A susceptibility locus at chromosome 3p21 linked to familial nasopharyngeal carcinoma. Cancer Res, 64, 1972-74. https://doi.org/10.1158/0008-5472.CAN-03-3253
  38. Yoshizaki T, Kondo S, Wakisaka N, et al (2013). Pathogenic role of epstein-barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma. Cancer Lett, 337, 1-7 https://doi.org/10.1016/j.canlet.2013.05.018
  39. Young LS, Rickinson AB (2004). Epstein - Barr virus: 40 years on. Nature, 4, 757-58.
  40. Zhang D, Mao Y, Xiong L, et al (2013). Characterization of human Fab antibody fragments specific to LMP1 (HLEAFab) in nasopharyngeal carcinoma for potential molecular diagnosis and therapeutic applications. Oncol Let, 5, 1694-98. https://doi.org/10.3892/ol.2013.1219