Detection of Hepatitis C Virus RNA Sequences in B-Cell Non-Hodgkin Lymphoma

Abstract

Serologic testing shows that hepatitis C virus (HCV) may have a role in the pathogenesis of B-cell non-Hodgkin lymphomas (B-cell NHLs). We tried to demonstrate HCV RNA sequences in paraffin-embedded tissue from B-cell NHLs by reverse-transcription double polymerase chain reaction (RT-PCR) and Southern blotting. We studied 31 consecutive cases of B-cell NHLs; lymph nodes from 32 patients with diseases other than B-cell NHL were negative controls. Positive-strand HCV RNA was tested with primers for the 5' untranslated region. Replicative negative strand HCV RNA was tested with strand-specific RT-PCR for the 5' untranslated region. Immunohistochemical staining for HCV was done using an antibody to HCV core protein. Positive-strand HCV RNA was detected in 8 patients with B-cell NHL; negative-strand HCV RNA was detected in 6 of these cases, indicating viral replication. All control cases were negative for HCV RNA. Immunohistochemistry showed no staining of lymphoma cells for HCV core proteins in any case. HCV and B-cell NHLs may be associated. RT-PCR on paraffin-embedded lymphoma tissue is an alternative method of testing for HCV. The value of immunohistochemistry could not be ascertained. The exact role of HCV in the pathogenesis of B-cell NHL needs to be studied further.

Detection of hepatitis C virus RNA in paraffin‐embedded tissues from patients with non‐Hodgkin's lymphoma

“…Besides, an important association has been demonstrated between HCV and lymphoproliferative disorders. Many studies have shown an increased prevalence of HCV infection in patients with B-cell non-Hodgkin's lymphoma (B-NHL), and the prevalence is between 9% and 32% [2][3][4][5][6][7][8][9][10]. In these studies, HCV has been tested serologically, but today the prevalence of HCV in lymphoproliferative disorders is not known.…”

B Cells in Chronically Hepatitis C Virus-Infected Individuals Lack a Virus-Induced Mutation Signature in theTP53,CTNNB1, andBCL6Genes

“…Notably, mutations in TP53, CTNNB1, and BCL6 were also identified in peripheral blood mononuclear cells (PBMC) of HCV-positive patients (12), although only about 10% of PBMC are B cells. As TP53 is a tumor suppressor gene and BCL6 and CTNNB1 are protooncogenes, mutations in these genes might be of pathogenetic relevance.Regarding the reported mutagenic effect of HCV, it should be mentioned that it is still controversially discussed whether HCV indeed infects B cells and induces mutations by a hit-and-run mechanism, or whether the effects seen are due to the binding of HCV to costimulatory receptors expressed on the surface of B cells, such as CD81 (17)(18)(19)(20)(21)(22)(23)(24).In the present work, we aimed to clarify whether the mutagenic effect of HCV on TP53, CTNNB1, and BCL6 is detectable in B cells of chronically HCV-infected patients, and hence might represent a main factor for B-cell lymphoproliferative diseases in such patients. …”

“…Regarding the reported mutagenic effect of HCV, it should be mentioned that it is still controversially discussed whether HCV indeed infects B cells and induces mutations by a hit-and-run mechanism, or whether the effects seen are due to the binding of HCV to costimulatory receptors expressed on the surface of B cells, such as CD81 (17)(18)(19)(20)(21)(22)(23)(24).…”

Induction of Interleukin-6 by Hepatitis C Virus Core Protein in Hepatitis C–Associated Mixed Cryoglobulinemia and B-Cell Non–Hodgkin's Lymphoma

“…MC is considered to be a benign B-cell proliferative disorder with clonal expansion of distinct B cells that can eventually turn into frank B-cell malignancy (3). Indeed, several groups have shown an increased incidence of B-cell nonHodgkin's lymphoma (B-NHL) in patients with chronic HCV infection (4), and an increased prevalence of HCV infections in patients with B-NHL has been reported (5,6). The hypothesis of an association between B-NHL and HCV infection is further supported by the observation that eradication of HCV by treatment with IFN-a and ribavirin could induce complete remission of splenic lymphomas with villous lymphocytes in seven of nine patients with chronic hepatitis C, whereas the same treatment had no effect in six patients with lymphomas who were HCV negative (7).…”