Gastrointestinal cancers reactive for the PAb416 antibody against JCV/SV40 T-Ag lack JCV DNA sequences while showing a distinctive pathologic profile

Aim: Immunohistochemical and molecular studies have suggested an oncogenic role for JCV in gastrointestinal carcinomas, but at least in colorectal cancers, the data are far from being unambiguous. Methods: Two large series of formalin-fixed paraffin-embedded gastric and colorectal cancers were analysed for the expression of JCV large T Antigen (T-Ag) with a panel of five antibodies, and for the presence of T-Ag DNA sequences using two PCR systems. Results: Intense nuclear staining was observed in 54/116 (46%) colorectal, and in 92/234 (39%) gastric cancers, using the PAb416 monoclonal antibody against large T-Ag. In colorectal cancers, PAb416-positivity was directly related to the presence of chromosomal instability, lymph node metastases and a more advanced tumour stage, and inversely related to proximal tumour site and the presence of microsatellite instability (MSI). In gastric cancers, the glandular histotype, the presence of lymph node metastases, a low frequency of MSI and EBV infection, and a worse prognosis were significantly associated with PAb416 immunoreactivity. Moreover, at both these sites, PAb416 expression was significantly associated with p53 nuclear accumulation. No positivity was obtained with all the other four anti-T-Ag-antibodies, and molecular analysis failed to demonstrate the presence of JCV DNA sequences in tested cases. Conclusions: Our immunohistochemical and molecular results do not support the idea that JCV T-Ag has a role in gastrointestinal carcinogenesis. It is possible that PAb416, besides binding the viral protein, may cross-react with a hitherto undefined protein whose expression is associated with a distinct pathological profile and, at least in gastric cancers, with worse prognosis.