Karsinoma Nasopharynx dan infeksi EBV di Indonesia; analisis aspek klinis, Patologi dan Biomolekular

Authors

  • Harianto Notopuro Department of Biochemistry, School of Medicine and Tropical Disease Centre Airlangga University, Surabaya.
  • Widodo A Kentjono Department of Ear, Nose and Throat, School of Medicine, Airlangga University and Dr Soetomo Hospital, Surabaya.
  • Retno Handajani Department of Biochemistry, School of Medicine and Tropical Disease Centre Airlangga University, Surabaya.
  • Paulus B Notopuro Department of Clinical Pathology, School of Medicine, Airlangga University and Dr Soetomo Hospital, Surabaya.

https://doi.org/10.33476/jky.v16i2.239

Keywords:

EBV, HPV, LMP-1 DNA, PCR, Nasopharynx Carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a unique epithelial malignancy that occurs at a high frequency in certain regions of Southeast Asia. Previous study revealed the association between Epstein Barr Virus (EBV) and to a lesser extent, Human Papilloma Virus (HPV) with NPC. The role of the EBV in the pathogenesis of NPC was further supported by the recovery response of the tumor cells after being treated with EBV-specific T lymphocytes. The present study aims to determine the frequency distribution of EBV infection among the pathologically confirmed NPC patients and healthy control in Surabaya, Indonesia. The presence of Human Papilloma. Virus infection (HPV) was also analysed. The results indicated that EBV DNA existed in the 88% of the nasopharyngeal tissue biopsies of 25 NPC patients and none in the 10 healthy controls, and the difference was statistically significant.Analysis of the mononuclear cells of peripheral blood revealed that 60% of the 25 NPC patients carried EBV DNA whereas in control group 20% was found to be positive and the difference was statistically significant. Although a high positive rate EBV-DNA was detected in NPC patients, additional environmental and genetic factors must still be considered. Nevertheless, no HPV-DNA was detected from mononuclear cells of peripheral blood and nasopharyngeal tissue of the two groups. By this study there was no coexistence between the infection of EBV and HPV which promote carcinogenesis in NPC. Analysis using LMP1-DNA in tumor cell biopsies indicated that 72% of the NPC patients yielded PCR products and none of the healthy control, the difference was statistically significant. In conclusion the findings confirm the tight association between the EBV and NPC in Indonesia and that the specific presence of LMP1-DNAs in the tumor cells strongly indicates the important role of EBV in the pathogenesis of NPC. Coexistence of EBV and HPV infections was not found in NPC cases in Indonesia.

References

Bahnassy AA, Zekri AR, Houssini SE, Khalid HM 2003. Epstein Barr Virus in Head and Neck Carcinoma in Egypt. J of the Egyptian Nat Cancer Inst, Vol 15, No 4, 349-362.

Chen ML, Tsai CN, Liang CL, Shu Ch, Huang CR, Sulitzeanu E 1992. Cloning and characterization of the latent membrane protein (LMP) of a specific Epstein Barr virus variant derived from the nasopharyngeal carcinoma in Taiwanese population. Oncogene 7:2131-3140.

Dickens P, Srivastava G, Liu YT 1992. Human papilloma virus 16/18 and nasopahryngeal carcinoma. J Clin Pathol 74:390393.

Gissmann L, Wolink L, Ikenberg H 1983. Human papilloma virus type 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci USA 80: 560-563.

Ho JHC 1972. Current knowledge of the epidemiology of nasopharyngeal carcinoma, in oncogenesis and Herpes viruses. IARC, Lyon: 357-365.

Hu LF, Zubarovsky ER, Chen F, Cao SL, Enberg I, Kein G 1991. Isolation and sequencing of the Epstein Barr virus BNLF1 gene (LMP1) from a chinese nasopharyngeal carcinoma. J Gen Virol 72: 2399-2409.

Hu Lf, Chen F, Zheng X, Ernberg I Cao SL, Christensson B 1993. Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane protein LMP1. Oncogene 8:1575-1583.

Jin CL, Wen YW, Kuang YC, Yau HW 2004. Quantification of Plasma Epstein Barr Virus DNA in Patients with Advanced Nasopharyngeal Carcinoma. N Eng J Med 350; 24: 2461-2470.

Kieff E 1996. Epstein Barr virus and its replication. Virology 3rd Ed Lippincot Raven Publisher Philadelphia: 2343-2396.

Knecht H, Bachmann E, Brousset P, Rothernberger S, Einsele H, Lestou VS 1995. Mutational hot spots within carboxyl terminal region of the LMP1 oncogene of Epstein Barr virus are frequent in lymphoproliferative disorders. Oncogene 10:523-528

Kuo WR, Chang CS, Lee CP, Lee KW, Tsai SM 1996. Detection of EBV in tumor tissue and peripheral blood by polymerase chain reaction in patients with nasopharyngeal carcinoma. Kaoshiung J Med Sci 12:613-618.

Kuo TT, Tsang NM 2001. Salivary gland type Nasopharyngeal Carcinoma: A Histologic, Immunohistochemical and Epstein Barr Virus study of 15 cases including a Psammomatous Mucoepidermoid Carcinoma. Am J of Surgical Path, Vol 25 No: 1: 80-86.

Lanier A, Bender T, Talbot M 1980. Nasopharyngeal carcinoma in Alaskan Eskimos, Indians and Aleuts: a review of cases and study of Epstein Barr virus, HLA and environmental risk factor. Cancer 46: 2100-2106

Liebowitz D 1994. Nasopharyngeal carcinoma: the Epstein Barr virus association. Semin Oncol 21:376-381.

Li SN, Chang YS, Liu ST 1996. Effect of a 10 amino acid deletion on the oncogenic activity of latent membrane protein 1 of Epstein Barr virus. Oncogene 12: 3129-2133.

Lin JC, Chen KY, Wang WY, Jan JS 2001. Detection of Epstein Barr Virus DNA in the peripheral Blood Ceels of patients with Nasopharyngeal Ca relationship with distant metastasis and survival. J of Clin Oncology, Vol 19, NO 10: 2607-2615.

Macdiarmid J, Stevenson D, Campbell DH, Wilson JB 2003. The latent membrane protein 1 of Epstein Barr virus and loss of the INK 4a locus: paradoxes resolve to cooperation I carcinogenesis in vivo. Carcinogenesis Vol 24, No 7: 12091218.

Mounts PSK, Kashima H 1982. Viral etiology of juvenile and adult onset squamous papilloma of the larynx. Proc Natl Acad Sci USA 79:5425-5429.

Muir CS 1971. Nasopahryngeal carcinoma in non chinese populations with special reference to Southeast Asia and Africa. Int J Cancer: 8: 351-363.

Muir CS, Waterhouse J, Mack T, Powell J, Whelan S 1987. Cancer incidence in five continents. IARC Sci Publ 88: 1-97.

Ping CP, Ngan MT, Chen KT, Sheng PH 2004. Prevalence of LMP-1 gene in tonsils and non-neoplastic nasopharyng by nest polymerase chain reaction in Taiwan. Head & Neck, Vol 26 No: 7: 619-624.

Raab-Traub N 1989. The human DNA tumor viruses : Human papilloma virus and Epstein Barr virus. Cancer Treat Res 47: 285-302.

Rassekh CH, Rady PL, Arany I, Tyring SK, Knudsen S, Calhoun KH, Seikaly H 1998. Combined Epstein Barr virus and human papilloma virus infection in nasopahryngeal carcinoma. Laryngoscope 108:362-367.

Telenti A, Marshall WF, Smith TF 1990. Detection of Epstein Barr virus by polymerase chain reaction. J of Clin Micro, Oct 1990: 2187-2190.

Tsang NM, Chang KP, Lin SY, Hao SP, Tseng CK 2003. Detection of Epstein Barr Virus- derived Latent Membran Protein 1 Gene in various Head and Neck Cancers: Is it specific for Nasopharyngeal Carcinoma?. The Laryngoscope Vol 113, No 6: 1050-1054.

Tsutsumi K, Nakajima T, Gotoh M 1989. In situ Hybridization and immunohistochemical study of human papillomas. Laryngoscope 99:80-85.

Tung YC, Lin KH, Chu PY, Hsu CC 1999. Detection of human papilloma virus and Epstein Barr virus DNA in nasopharyngeal carcinoma by polymerase chain reaction. Kaoshiung J Med Sci 15: 256-262.

Turazza E, Lapena A, Spovieri O, Torres CP, Gurncharri C, Maciel A, Luna B 1997. Low risk human papillomavirus type 6 and 11 associated with carcinoma of the genital and upper aero digestive tract. Acta Obstet Gynecol Scan 76: 271-276.

Walter M, Palance JM, Peiper SC 1992. Epstein Barr virus detection in neck metastases by polymerase chain reaction. Laryngoscope 102, May: 481-485.

Wilson JB, Weinberg R, Johnson R, Yuspa S, Levine AJ 1990. Expression of the BNLF1 oncogene of Epstein Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Cell 61:1315-1327.

Zheng N, Yuan L, Hu F, Chen G, Christensson 1994. Effect of B lymphocyte and NPC derived EBV-LMP1, gene expression on in vitro growth and differentiation of human epithelial cells. Int J Cancer 57: 747-753.

Downloads

Published

2008-06-16

Issue

Section

Research Articles