Replication status as a marker for predisposition for lymphoma in patients with chronic hepatitis C with and without cryoglobulinemia

Objective Essential mixed cryoglobulinemia (EMC) type II is associated with hepatitis C virus (HCV) in 90% of the patients with this disorder. A significant subset of these patients is at risk to develop non-Hodgkin lymphoma (NHL). The objective of this study was to examine whether the presence of EMC, a presumably premalignant step of lymphoproliferation, is associated with changes in the replication state of normal structural genes. Materials and Methods The study group included three subgroups: (1) seven patients with HCV without EMC; (2) eight patients with HCV associated with EMC. 3. Seven patients with follicular lymphoma; and (3) six healthy individuals served as control group. Monocolor fluorescent in situ hybridization (FISH) with probes to p53, RB-1, and 21q22 was applied to leukocytes nuclei for the evaluation of replication timing. Results Asynchronous replication (SD) rate was similar in patients with NHL and those with HCV associated with EMC and both are significantly higher when compared to patients with HCV without EMC and to normal controls (p < 0.01) for each comparison. This held true for all studied loci (21q22, RB-1, and p53). Patients infected by HCV (but without EMC) had a significantly higher rate of asynchronous pattern in comparison with healthy controls (p < 0.01). Conclusions Patients with a “premalignant” clinical condition HCV with EMC already demonstrate asynchronous type of replication which is similar to patients who already have an established malignant disease (i.e., NHL). In the future, replication may be used to assess the risk of malignant transformation in patients with “benign” proliferation.