Aggressive forms of non-Hodgkin's lymphoma in two patients bearing coinfection of Epstein-Barr and hepatitis C viruses.
Although epidemiologic and experimental data suggest an etiopathogenetic role for both hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection in development of B-cell non-Hodgkin's lymphoma (NHL), potential interactions between EBV and HCV during progression of B-cell NHL have not yet been fully investigated. In the present study, tumor biopsy specimens from patients with both B-cell NHL and chronic HCV infection (HCV(+)) were analyzed for the presence of EBV-encoded RNA (EBER) by in situ hybridization (ISH). VH and VL gene segments were amplified from tumor biopsy specimen DNA by PCR. EBV infection (EBV(+)) was detected in tumors from 2 of 31 (6%) HCV(+) B-cell NHL patients. Clinical histories of these two EBV(+)/HCV(+) B-cell NHL patients indicated a particularly aggressive course of disease. Chemotherapy failed to induce long lasting remission for either of these EBV(+)/HCV(+) B-cell NHL patients. Amplification of CDR3 of the Ig heavy chain gene from DNA isolated from each EBV(+)/HCV(+) B-cell NHL indicated the presence of monoclonal B-cell expansion. Rearrangement of Ig genes in neoplastic B-cell clones from both EBV(+)/HCV(+) patients was similar to that previously reported for EBV(-)/HCV(+) B-cell NHL patients. Additionally, neoplastic B-cell clones from these two EBV(+)/HCV(+) B-cell NHL patients did not exhibit intraclonal variation. Previous studies have demonstrated that intraclonal variation is common among neoplastic B-cell clones from EBV(-)/HCV(+) patients. EBV infection may have prevented evolution of variant neoplastic B-cell clones by suppressing antibody affinity maturation. Together, these data suggest that EBV infection may cooperate with HCV infection during progression of B-cell NHL in immunocompetent individuals. Such an interaction may accelerate the course of disease in B-cell NHL patients.
Libra
Massimo
M
Division of Experimental Oncology 1, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, IRCCS, Via Pedemontana Occidentale 12, I-33081 Aviano, PN, Italy.
Gloghini
Annunziata
A
De Re
Valli
V
Rupolo
Maurizio
M
Navolanic
Patrick M
PM
Gasparotto
Daniela
D
Stivala
Franca
F
Spina
Michele
M
Boiocchi
Mauro
M
Carbone
Antonino
A
D000368:Aged; D002471:Cell Transformation, Neoplastic; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D007121:Immunocompetence; D016393:Lymphoma, B-Cell / Q000473:pathology* / Q000821:virology*; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology* / Q000821:virology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis
D004279:DNA, Viral