Gastrointestinal cancers reactive for the PAb416 antibody against JCV/SV40 T-Ag lack JCV DNA sequences while showing a distinctive pathologic profile
- Anna Maria Chiaravalli1,
- Erika Longhi2,
- Davide Vigetti3,
- Francesca Isabella De Stefano4,
- Sara Deleonibus3,
- Carlo Capella4,
- Enrico Solcia5,
- Carlo Parravicini6
- 1Anatomic Pathology Unit, Ospedale di Circolo and University of Insubria, Varese, Italy
- 2Department of Clinical Sciences, University of Milano c/o U.O. Anatomia Patologica, ‘L.Sacco’ University Hospital, Milano, Italy
- 3Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy
- 4Department of Surgical and Morphological Sciences, Anatomic Pathology Unit, University of Insubria and Ospedale di Circolo, Varese Italy
- 5Department of Human Pathology, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- 6U.O. Anatomia Patologica, ‘L.Sacco’ University Hospital, Milano, Italy
- Correspondence to Anna Maria Chiaravalli, Anatomic Pathology Unit, Ospedale di Circolo and University of Insubria, viale Borri 57, 21100 Varese, Italy;
- Received 29 August 2012
- Revised 29 August 2012
- Accepted 29 August 2012
- Published Online First 25 September 2012
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.