We evaluated the association of nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) in Spanish patients, and studied the expression of EBV products (latent membrane protein–1 [LMP-1] and ZEBRA proteins) by NPC cells and its possible prognostic value. In situ hybridization (ISH) for EBV-encoded nonpolyadenylated RNAs (EBERs) and immunohistochemical expression of LMP-1 and ZEBRA proteins by immunohistochemistry were examined in formalin-fixed, paraffin-embedded NPC specimens from 30 patients, and a survival analysis was done by the Kaplan-Meier method. We detected EBERs by ISH in 96.67% of the NPC cases, and detected expression of LMP-1 in 43.33% of the NPC cases and expression of ZEBRA protein in 6.67% of the NPC cases. We conclude that ISH for expression of EBERs is an adequate method for detection of EBV in NPC. LMP-1 is not frequently expressed in NPC cells (43.33%). Most NPC cells carry a latent EBV infection. LMP-1 expression might have worsened the prognosis of NPC in our series.
AnagnostopoulosIHummelM. Epstein-Barr virus in tumours. Histopathology1996;29:297–315.
2.
VasefMAFerlitoAWeissLM. Nasopharyngeal carcinoma, with emphasis on its relationship to Epstein-Barr virus. Ann Otol Rhinol Laryngol1997;106:348–56.
3.
HoweJGSteitzJA. Localization of Epstein-Barr virus–encoded small RNAs by in situ hybridization. Proc Natl Acad Sci USA1986;83:9006–10.
4.
Thorley-LawsonDAMiyashitaEMKhanG. Epstein-Barr virus and the B cell: That's all it takes. Trends Microbiol1996;4:204–8.
5.
HuL-FChenFZhenQ-F. Differences in the growth pattern and clinical course of EBV-LMP1 expressing and non-expressing nasopharyngeal carcinomas. Eur J Cancer1995;31A:658–60.
6.
SamoszukM. Rapid detection of Epstein-Barr viral DNA by nonisotopic in situ hybridization: Correlation with the polymerase chain reaction. Am J Pathol1991;96:448–53.
7.
Vera-SempereFJBurgosJSBotellaMSMoreraC. Comparative analysis of Epstein-Barr virus (EBV) detection by nested-PCR and non-isotopic in situ hybridization in nasopharyngeal carcinoma. Clin Chim Acta1998;271:119–32.
8.
SamCKBrooksLANiedobitekGYoungLSPrasadURickinsonAB. Analysis of Epstein-Barr virus infection in nasopharyngeal biopsies from a group at high risk of nasopharyngeal carcinoma. Int J Cancer1993;53:957–62.
9.
GulleyMLAminMANichollsJM. Epstein-Barr virus is detected in undifferentiated nasopharyngeal carcinoma but not in lymphoepifhelioma-like carcinoma of the urinary bladder. Hum Pathol1995;26:1207–14.
10.
PathmanathanRPrasadUChandrikaGSadlerRFlynnKRaab-TraubN. Undifferentiated, nonkeratinizing, and squamous cell carcinoma of the nasopharynx. Variants of Epstein-Barr virus–infected neoplasia. Am J Pathol1995;146:1355–67.
11.
NiedobitekGHansmannMLHerbstH. Epstein-Barr virus and carcinomas: Undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus. J Pathol1991;165:17–24.
12.
MuronoSYoshizakiTTanakaSTakeshitaHParlCSFurukawaM. Detection of Epstein-Barr virus in nasopharyngeal carcinoma by in situ hybridization and polymerase chain reaction. Laryngoscope1997;107:523–6.
13.
ChaoT-YChowK-CChangJ-Y. Expression of Epstein-Barr virus-encoded RNAs as a marker for metastatic undifferentiated nasopharyngeal carcinoma. Cancer1996;78:24–9.
14.
Hamilton-DutoitSJPallesenG. Detection of Epstein-Barr virus small RNAs in routine paraffin sections using nonisotopic RNA/RNA in situ hybridization. Histopathology1994; 25:101–11.
15.
TsaiSTJinYTSuIT. Expression of EBER1 in primary and metastatic nasopharyngeal carcinoma tissues using in situ hybridization: A correlation with WHO histologic subtypes. Cancer1996;77:231–6.
16.
KouvidouCKanavarosPPapaioannouD. Expression of bcl-2 and p53 proteins in nasopharyngeal carcinoma. Absence of correlation with the presence of EBV encoded EBER 1-2 transcripts and latent membrane protein-1. JCP Clin Mol Pathol1995;48:M17–M22.
17.
WuTCMannRBEpsteinJI. Abundant expression of EBER1 small nuclear RNA in nasopharyngeal carcinoma: A morphologically distinctive target for detection of Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens. Am J Pathol1991;138:1461–9.
18.
DictorMSivénMTennvallJRambechE. Determination of nonendemic nasopharyngeal carcinoma by in situ hybridization for Epstein-Barr virus EBER1 RNA: Sensitivity and specificity in cervical node metastasis. Laryngoscope1995;105: 407–12.
19.
WolfHBogedainCSchwarzmannF. Epstein-Barr virus and its interaction with the host. Intervirology1993;35:26–39.
20.
LuQ-LEliaGLucasSAlejo-ThomasJ. bcl-2 Protooncogene expression in Epstein-Barr virus-associated nasopharyngeal carcinoma. Int J Cancer1993;53:29–35.
21.
Vera-SempereFJBurgosJSBotellaMSCordobaJGobernadoM. Immunohistochemical expression of Epstein-Barr virus–encoded latent membrane protein (LMP-1) in paraffin sections of EBV-associated nasopharyngeal carcinoma in Spanish patients. Eur J Cancer B Oral Oncol1996;32B:163–8.
22.
JiwaNMOudejansJJDukersDF. Immunohistochemical demonstration of different latent membrane protein-1 epitopes of Epstein-Barr virus in lymphoproliferative diseases. J Clin Pathol1995;48:438–42.
23.
SantónAManzanalACampoEBellasC. Deletions in the Epstein-Barr virus latent membrane protein–1 oncogene in Hodgkin's disease. JCP Clin Mol Pathol1995;48:M184–M188.
24.
BrooksLYaoQYRickinsonABYoungLS. Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: Coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol1992;66:2689–97.
25.
CochetCMartel-RenoirDGrunewaldV. Expression of the Epstein-Barr virus immediate early gene, BZLF1, in nasopharyngeal carcinoma tumor cells. Virology1993;197:358–65.
26.
Martel-RenoirDGrunewaldVTouitouRSchwaabGJoabI. Qualitative analysis of the expression of Epstein-Barr virus lytic genes in nasopharyngeal carcinoma biopsies. J Gen Virol1995;76:1401–8.
27.
PaganoJS. The Epstein-Barr virus and nasopharyngeal carcinoma [Editorial]. Cancer1994;74:2397–8.
28.
ShanmugaratnamKChanSHde ThéG. Histopathology of nasopharyngeal carcinoma: Correlations with epidemiology, survival rates and other biological characteristics. Cancer1979;44:1029–44.
29.
HsuH-CChenC-LHsuM-MLynnT-CTuS-MHuangS-C. Pathology of nasopharyngeal carcinoma. Proposal of a new histologic classification correlated with prognosis. Cancer1987;59:945–51.
30.
HoJHC. An epidemiologic and clinical study of nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys1978;4:183–98.
31.
HordingUNielsenHWAlbeckHDaugaardS. Nasopharyngeal carcinoma: Histopathological types and association with Epstein-Barr virus. Eur J Cancer B Oral Oncol1993;29B:137–9.
32.
NiedobitekGYoungLSSamCKBrooksLPrasadURickinsonAB. Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferentiated nasopharyngeal carcinomas. Am J Pathol1992;140:879–87.
33.
StewartJPArrandJR. Expression of the Epstein-Barr latent membrane protein in nasopharyngeal carcinoma biopsy specimens. Hum Pathol1993;24:239–42.
34.
ZhengXHuLChenFChristenssonB. Expression of Ki67 antigen, epidermal growth factor receptor and Epstein-Barr virus-encoded latent membrane protein (LMP1) in nasopharyngeal carcinoma. Eur J Cancer B Oral Oncol1994;30B:290–5.
35.
AgathanggelouANiedobitekGChenRNichollsJYinWYoungLS. Expression of immune regulatory molecules in Epstein-Barr virus–associated nasopharyngeal carcinomas with prominent lymphoid stroma. Evidence for a functional interaction between epithelial tumor cells and infiltrating lymphoid cells. Am J Pathol1995;147:1152–60.
36.
YaoMOhshimaKSuzumiyaJKumeTShiroshitaTKikuchiM. Interleukin-10 expression and cytotoxic-T-cell response in Epstein-Barr–virus–associated nasopharyngeal carcinoma. Int J Cancer1997;72:398–402.
37.
PathmanathanRPrasadUSadlerRFlynnKRaab-TraubN. Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N Engl J Med1995;333:693–8.
38.
KhannaRBurrowsSRKurillaMG. Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: Implications for vaccine development. J Exp Med1992;176:169–76.
39.
GulleyMLBurtonMPAllredDC. Epstein-Barr virus infection is associated with p53 accumulation in nasopharyngeal carcinoma. Hum Pathol1998;29:252–9.
40.
SchusterVPukropT. Epstein-Barr virus and nasopharyngeal cancer [Letter]. N Engl J Med1996;334:122–3.
41.
TsaiS-TJinY-TMannRBAmbinderRF. Epstein-Barr virus detection in nasopharyngeal tissues of patients with suspected nasopharyngeal carcinoma. Cancer1998;82:1449–53.
42.
HsiaoJRJinY-TTsaiS-T. EBER1 in situ hybridization as an adjuvant for diagnosis of recurrent nasopharyngeal carcinoma. Anticancer Res1998;18:4585–9.
