SV40 infection in human cancers

Simian virus 40 (SV40) is a monkey virus recently detected in a variety of human cancers such as mesothelioma, central nervous system (CNS) tumours and non-Hodgkin's lymphoma [1Go]. Despite a large body of data suggesting that SV40 is implicated in different tumours in humans, there are still controversies as to whether SV40 has a role in cancer development [2Go–4Go]. Morphological methods (in situ hybridization and immunohistochemistry) have been tested in a few studies, which only suggested that the detection of the virus, contrary to other oncogenic viruses, is not reproducible in routine diagnosis. A recent report by Lopez-Rios et al. [2Go] convincingly addressed the issue of SV40 infection in human mesothelioma [2Go]. Their demonstration pointed out a problem of PCR contamination to explain some results. With different approaches, we came to the same conclusion: SV40 has probably little to do with human cancers. Our experience was based on the use of highly sensitive immunohistochemistry with a monoclonal antibody against SV40 large T antigen (T-ag) applied on tissue sections from Hodgkin's and non-Hodgkin's lymphoma and CNS tumours [3Go, 4Go]. In one study [3Go], we failed to detect SV40 T-ag in a series of 82 cases of CNS tumours of various types including plexus choroid tumours and ependymomas. In a second study [4Go], we investigated a series of French and Canadian cases of Hodgkin's and non-Hodgkin's lymphoma with the same technology, i.e. with standard immunohistochemistry and a highly sensitive catalysed system amplification method (CSATM, Dako, Copenhagen, Denmark). The latter technique has, on average, 50-fold greater sensitivity. Again, none of the cases of Hodgkin's lymphoma (n=250) or non-Hodgkin's lymphoma (n=232) scored positively, whilst two positive controls were labelled [3Go, 4Go].

To extend our study on SV40, we have tested a series of 100 cases of mesothelioma on standard paraffin sections (n=65) and tissue microarrays (n=35). All cases were prepared under the same conditions (fixed 10% buffered formalin and embedded in paraffin). Repeatedly, our results remained negative despite the fact that one-third of the cases had been considered positive with PCR [5Go]. Using tissue array methodology, we then investigated different types of cancers from lung [small-cell carcinoma (n=15) and non-small-cell carcinoma (n=43)], digestive tract [gastric adenocarcinoma (n=13), colon adenocarcinoma (n=20)], thyroid [papillary carcinoma (n=30), follicular carcinoma (n=10)], prostate [adenocarcinoma (n=21)] and thymus [thymoma (n=13), thymic carcinoma n=6)] for SV40 T-ag. Not a single cell could be detected in these tissues. In parallel, we were unable to detect SV40 T-ag in different tissue arrays of normal organs. In particular, we were unable to detect cells infected with the ubiquitous BK virus in normal kidneys (n=10) and in clear-cell carcinomas (n=12), since the anti-Tag antibody used cross-reacts with this virus.

One important argument against the implication of SV40 in human oncogenesis is that this virus infects monkeys without induction of any type of cancer in this species. Indeed, monkeys are genetically closer to humans than mice. In the latter, the observation of SV40 driven cancers is frequently the result of experiments that induce an up-regulation of viral genes.

P. Brousset1,*, J. Sabatier2 and F. Galateau-Sallé3

1 Department of Pathology, Purpan Hospital and INSERM U563 (CPTP), CHU Purpan, Toulouse; 2 Department of Neurosurgery, Purpan Hospital, Toulouse; 3 Department of Pathology, CHU Caen, France

(*Email: brousset.p{at}chu-toulouse.fr).

References

1. Klein G, Powers A, Croce C. Association of SV40 with human tumors. Oncogene 2002; 21: 1141–1149.[CrossRef][ISI][Medline]

2. Lopez-Rios F, Illei PB, Rusch V, Ladanyi M. Evidence against a role for SV40 infection in human mesotheliomas and high risk of false-positive PCR results owing to presence of SV40 sequences in common laboratory plasmids. Lancet 2004; 364: 1157–1166.[CrossRef][ISI][Medline]

3. Sabatier J, Uro-Coste E, Benouaich A et al. Immunodetection of SV40 large T antigen in human central nervous system tumours. J Clin Pathol, in press.

4. Brousset P, De Araujo V, Gascoyne RD. Immunohistochemical investigation of SV40 large T antigen in Hodgkin and non Hodgkin's lymphoma. Int J Cancer 2004; 112: 533–535.[CrossRef][ISI][Medline]

5. Galateau-Salle F, Bidet P, Iwatsubo Y et al. SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma, and non-malignant pulmonary diseases. J Pathol 1998; 184: 252–257.[CrossRef][ISI][Medline]





This Article
Full Text (PDF)
All Versions of this Article:
16/7/1212    most recent
mdi202v1
E-letters: Submit a response
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Brousset, P.
Articles by Galateau-Sallé, F.
PubMed
PubMed Citation
Articles by Brousset, P.
Articles by Galateau-Sallé, F.