Presence of JC virus DNA in the tumor tissue and normal mucosa of patients with sporadic colorectal cancer (CRC) or with positive family history and Bethesda criteria.

INTRODUCTION: JC virus (JCV) may infect the gastrointestinal tract in childhood, and, by encoding a gene for T-antigen (T Ag), can initiate chromosomal instability in epithelial cells.

AIM: We looked for JCV DNA in the cancer tissue of patients with sporadic colorectal cancer (CRC, Group A) and with positive family history and Bethesda criteria (Group B). We hypothesized that the role of JCV may be different between these two groups.

METHODS: Fifty-six patients were randomly selected from our database, 30 in Group A and 26 in Group B. DNA was isolated from the tumor, normal mucosa, and plasma, and JCV DNA sequences were looked for with specific polymerase chain reaction (PCR) assays for T Ag primers. Immunohistochemistry for hMLH1, hMSH2, hMSH6, and PMS2 was performed on paraffin-embedded tissue.

RESULTS: In Group A, T Ag was demonstrated in 6 (20.00%) and 3 (10.00%) of the tumors and adjacent normal mucosa, respectively (P = 0.094). In Group B, the corresponding observations were 10 (38.46%) and 6 (23.07%), respectively (P < 0.001). Immunohistochemistry for hMLH1, hMSH2, hMSH6, and PMS2 was performed in all of the Group A and B patients. All patients of Group A (100%) showed expression of these proteins, while only 19 patients of Group B did so (73.1%), P = 0.009. JCV T Ag DNA was found in 20, 28.5, and 42.1% of the tumors in Group A, Group B with negative staining for DNA repair genes, and Group B with a positive staining, respectively (NS).

CONCLUSION: CRC patients with positive family history have a higher incidence of JCV T Ag, but this did not correlate with specific DNA repair gene mutations. We could not conclude that, on the background of genetic mutation in one of the DNA repair genes, JCV acts as the missing link in the chain of events leading to CRC.