Epstein–Barr virus infection in colorectal neoplasms associated with inflammatory bowel disease: detection of the virus in lymphomas but not in adenocarcinomas

Abstract

Epstein-Barr virus (EBV) is associated with several lymphoid and epithelial human malignancies. The latter include gastric adenocarcinomas, while sporadic colorectal adenocarcinomas (CRCs) have been reported to be EBV-negative. Recently, increased numbers of EBV-infected B lymphocytes have been detected in intestinal mucosal samples affected by ulcerative colitis (UC) and, to a lesser extent, Crohn's disease (CD). Both CRC and colorectal non-Hodgkin's lymphoma (NHL) are recognized complications of inflammatory bowel disease (IBD), but it is unclear to what extent EBV contributes to the development of these neoplasms. Seventeen cases of IBD-associated CRC and nine cases of IBD-associated colorectal NHL were therefore studied for the presence of EBV by in situ hybridization. EBV-positive cases were further studied for the expression of the EBV-encoded nuclear antigen (EBNA) 2 and the latent membrane protein (LMP) 1 of EBV by immunohistochemistry. Four out of seven cases of colorectal NHL associated with UC were shown to be EBV-positive. In addition, two of two colorectal NHLs developing in patients with CD were EBV-positive. Of the EBV-positive lymphomas, three displayed a pattern of EBV latent gene expression consistent with type I latency (EBNA2(-)/LMP1(-)), two a type II pattern (EBNA2(-)/LMP1(+)), and one a type III pattern (EBNA2(+)/LMP1(+)). These findings suggest that EBV infection is involved in the pathogenesis of a proportion of colorectal NHLs developing in IBD. Iatrogenic immunosuppression may contribute to the development of these lymphomas. By contrast, all 17 IBD-associated CRCs were EBV-negative, including a case of CRC occurring synchronously with an EBV-positive NHL. In conjunction with previous reports on sporadic CRCs, this suggests that EBV is not involved in the pathogenesis of CRC.

The risk of lymphoma and immunomodulators in patients with inflammatory bowel diseases: Results from a population-based cohort in Eastern Europe

“…The importance of infectious pathogens in CD is still debated, EBV is one of the most common pathogen which can be detected in colonic mucosa of CD patients. 29 Wong, et al, detected EBV in IBD associated lymphomas, but not in IBD associated CRC-s. 30 In addition, Dayharsh et al identified 18 IBD patients diagnosed with lymphoma at the Mayo Clinic, in Rochester, Minnesota, between 1985 and 2000. 31 Six patients diagnosed with lymphoma were on AZA or 6-MP.…”

Epstein-Barr Virus-associated Enteropathy as a Complication of Infectious Mononucleosis Mimicking Peripheral T-cell Lymphoma

“…Immunosuppressive therapy in IBD patients can reactivate latent EBV infections, which can lead to enteropathy (16). In particular, EBV-associated enteropathy frequently occurs during intensive immunosuppressive therapy in UC patients (16,17). In addition, enteropathy that is associated with the reactivation of latent EBV infections has also been reported to occur following both allogeneic stem cell transplantation and intestinal transplantation (18,19).…”

“…Immunosuppressive therapy in IBD patients can reactivate latent EBV infections, which can lead to enteropathy (16). In particular, EBV-associated enteropathy frequently occurs during intensive immunosuppressive therapy in UC patients (16,17).…”

The Role of Infectious Agents in Colorectal Carcinogenesis

“…Follow-up studies failed to show any evidence that EBV was detected at a significantly higher rate in colorectal carcinoma (Grinstein et al, 2002;Yuen et al, 1994), even in higher risk populations such as patients with ulcerative colitis (N.A. Wong et al, 2003). In the case of Cytomegalovirus (CMV), early limited studies have detected CMV genome in the colon carcinoma tissue, whereas controls from normal colons and cases of Crohn disease were negative (Huang & Roche, 1978;Hashiro et al, 1979).…”