Epstein-Barr viral infection in extranodal lymphoma of the head and neck: correlation with prognosis and response to treatment

• Published in: Histopathology 2006-04, Vol.48 (5), p.516-528
• Main Authors: Bahnassy, A A, Zekri, A-R N, Asaad, N, El-Houssini, S, Khalid, H M, Sedky, L M, Mokhtar, N M
• Format: Article
• Language: English
• Subjects: Adolescent; Aged; bcl-2 and Bax; bcl-2-Associated X Protein - analysis; Biological and medical sciences; Cell Line, Tumor; Child; Child, Preschool; EBV; Epstein-Barr virus; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - virology; Female; head and neck; Head and Neck Neoplasms - complications; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - classification; Herpesvirus 4, Human - genetics; Humans; Immunohistochemistry; In Situ Hybridization; Investigative techniques, diagnostic techniques (general aspects); Ki-67 Antigen - analysis; Ki67; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; lymphoma; Lymphoma - complications; Lymphoma - metabolism; Lymphoma - pathology; Male; Medical sciences; Middle Aged; p53; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prognosis; Proto-Oncogene Proteins c-bcl-2 - analysis; RNA, Viral - genetics; Survival Analysis; Treatment Outcome; Tumor Suppressor Protein p53 - analysis
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2006.02377.x

Aims : 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. Material and 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. Conclusion : 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.