title: Epstein-Barr viral infection in extranodal lymphoma of the head and neck: correlation with prognosis and response to treatment.
abstract: OBJECTIVE
  To determine the prevalence of Epstein-Barr virus (EBV) infection in primary extranodal lymphoma of the head and neck (PELHN) in immunocompetent patients. PELHN represents 16.18% of all lymphoma diagnosed at the National Cancer Institute, Cairo. Although EBV infection is highly associated with lymphoma in immunocompromised patients, the situation in immunocompetent patients is still unclear.
  
  
  METHODS
  The study included 50 PELHN (11 cases in the nose and paranasal sinuses, 11 in the nasopharynx, 13 in the tonsils, seven in the oropharynx and eight in the oral cavity), five reactive lymph nodes, 15 normal nasopharyngeal tissue and 25 throat washes of healthy subjects from Egypt. Cases and controls were assessed for the presence of EBV by polymerase chain reaction (PCR) and in situ hybridization techniques, the presence of 30 base pair deletion of the LMP-1 (del-LMP1) gene and for the expression of p53, Ki67, bcl-2 and Bax by immunohistochemistry. This was also correlated with the clinical outcome of patients.
  
  
  RESULTS
  EBV was detected in 90% and 70% of the cases using EBER in situ hybridization and PCR, respectively. All cases of nasal type lymphoma were positive for EBV. del-LMP1 gene was detected in 24/35 of EBV+ cases (68.6%), whereas 11 cases had wild-type variant either alone or mixed with del-LMP1. There was a significant difference in the frequency of del-LMP1 between lymphoma and normal tissues. Overexpression of Ki67, p53 and bcl-2 was detected in 78.1%, 62.5% and 20% of cases, whereas loss of Bax was detected in 18% of the cases. Multivariate analysis showed that only p53 overexpression, del-LMP1 variant and advanced disease stage are independent prognostic factors.
  
  
  CONCLUSIONS
  EBV infection is frequent in PELHN in Egypt. Possible pathogenic mechanisms involve deregulation of p53 and enhanced proliferation (as detected by high Ki67 index). The presence of del-LMP1 variants, p53 overexpression and advanced disease stage are poor prognostic factors associated with reduced survival and poor response to therapy.
authors.affiliation: Pathology Department, Menofya University, Cairo, Egypt. chaya2000@hotmail.com
authors.forename: A A
authors.initials: AA
authors.lastname: Bahnassy
authors.forename: A-R N
authors.initials: AR
authors.lastname: Zekri
authors.forename: N
authors.initials: N
authors.lastname: Asaad
authors.forename: S
authors.initials: S
authors.lastname: El-Houssini
authors.forename: H M
authors.initials: HM
authors.lastname: Khalid
authors.forename: L M
authors.initials: LM
authors.lastname: Sedky
authors.forename: N M
authors.initials: NM
authors.lastname: Mokhtar
mesh_terms: D000293:Adolescent; D000368:Aged; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000145:classification / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000032:analysis; D008223:Lymphoma / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: C106732:Epstein-Barr virus encoded RNA 2; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein