SV40 large T-antigen and human pleural mesothelioma. Screening by polymerase chain reaction and tyramine-amplified immunohistochemistry

Our plain-English summary of SV40 large T-antigen and human pleural mesothelioma. Screening by polymerase chain reaction and tyramine-amplified immunohistochemistry, by K. Dhaene, A. Verhulst, E. Van Marck (Virchows Archiv, 1999).

The study

• Authors: K. Dhaene, A. Verhulst, E. Van Marck
• Journal: Virchows Archiv
• Published: 1999;435(1):1-7
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

DNA-like sequences of the p53 and pRB-inactivating simian virus 40 large T-antigen (SV40 LTag) have recently been found in mesotheliomas in the United States and several European countries. Nuclear expression of SV40 LTag, possibly in concert with detectable telomerase activity, could be responsible for immortalisation of (pre)malignant clones, as suggested by the mesothelioma-specific latency period. Depending on the antibody used, different results have been observed regarding the subcellular expression of SV40 LTag in mesotheliomas with SV40 LTag-like DNA sequences. In this study, we screened 28 Belgian mesothelioma tumour samples for the presence of SV40 LTag-like DNA and its gene product by polymerase chain reaction amplification, using the SV.for3/SV.rev primer set, and by tyramine-amplified immunohistochemistry, using the pAb419 and the pAb101 SV40 LTag antibodies. Amplicons were found in 13 of the 28 (46%) mesotheliomas. Cytoplasmic, but no nuclear, staining was found in 10 of these 13 cases. Although our study confirms the presence of SV40 LTag-like DNA sequences in Belgian mesotheliomas, we did not detect nuclear expression of the viral oncoprotein, which makes a pathogenic role of SV40 LTag in mesothelioma carcinogenesis questionable.

In plain English

This laboratory study, which the authors described as a first screening test, looked for traces of simian virus 40 (SV40), a monkey virus, in tumour tissue from 28 patients with primary pleural mesothelioma. The patients were diagnosed between 1990 and 1997 at the University Hospital of Antwerp, Belgium. The study also tested 10 lung carcinomas. The article did not report the patients' asbestos exposure. Using PCR, DNA resembling the gene for the SV40 large T-antigen was found in 13 of the 28 (46%) mesotheliomas and in 1 of the 10 lung carcinomas, an adenocarcinoma. With one antibody, 13 mesotheliomas showed cytoplasmic staining, and 10 of these also had the viral DNA-like sequences. No lung carcinoma stained. A second, amplified staining method found no nuclear staining in any mesothelioma. The authors concluded that, although the DNA-like sequences were present, the lack of nuclear protein makes a role for SV40 in causing mesothelioma questionable. They noted that their series was small, that normal tissues were not examined, and that the origin and exact nature of the sequences remained undetermined.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of stored tumour tissue using PCR (DNA detection) and immunohistochemistry (protein staining), described by the authors as a first, preliminary screening test
• Who was studied: Tumour samples from 28 primary pleural mesotheliomas (21 frozen, 7 paraffin-embedded; 15 epithelial, 4 sarcomatous, 9 mixed type) from the files of the Department of Pathology, University Hospital of Antwerp, Belgium, diagnosed between 1990 and 1997. The mean patient age was 63 years, range 41 to 86. The study also included 10 bronchopulmonary carcinomas (5 squamous cell carcinomas and 5 adenocarcinomas) for comparison.
• Exposure: Presence of SV40 large T-antigen (LTag)-like DNA (PCR with the SV.for3/SV.rev primers) and of the LTag protein (antibodies pAb419 and pAb101, the latter with tyramine amplification) in tumour tissue. The article did not report asbestos exposure for these patients.
• Main results:
  • SV40 LTag-like DNA sequences were found in 13 of the 28 (46%) mesothelioma samples (10/21 frozen and 3/7 paraffin-embedded).
  • Among the 10 lung carcinomas, the SV40-like DNA band was seen in 1 adenocarcinoma; the other 9 were negative.
  • With the pAb419 antibody, 13 mesotheliomas showed strong cytoplasmic staining; no staining was detected in any of the lung carcinomas. The share of stained cells varied from 30% to 80%.
  • Of the 13 mesotheliomas with SV40-like DNA, 10 showed cytoplasmic staining but no nuclear staining.
  • No staining was found in 15 mesotheliomas, 12 of which were also PCR-negative; the remaining 3 were PCR-positive without detectable staining.
  • Using the pAb101 antibody with tyramine amplification (which stained nearly 100% of nuclei in the positive control cells), no nuclear staining was detected in any of the mesothelioma sections.
• The authors' conclusion: The authors concluded that their study confirmed SV40 LTag-like DNA sequences in Belgian mesotheliomas, but that the absence of nuclear expression of the viral protein makes a pathogenic role of SV40 LTag in mesothelioma questionable. They judged the presence of the LTag protein improbable in their cases and said their data do not constitute hard evidence. From their small series, they could only say that SV40 seems to be more common in mesothelioma than in lung carcinoma.
• Limitations the authors state:
  • The series was small.
  • Normal human tissues, including normal mesothelium and lung tissue, were not examined, so it is unresolved whether the virus is as common in normal tissue.
  • The authors could not attribute the SV40-like DNA to contaminated vaccines rather than a natural background source of infection.
  • The primers might have artificially amplified a tumour-specific cellular look-alike of LTag (or possibly sequences from other viruses such as BK virus); the exact nature of the amplified sequences remains to be determined.
  • The cytoplasmic staining seen with pAb419 may reflect cross-reactivity with the SV40 small t antigen, which awaits further investigation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: SV40, Pleural Mesothelioma, Immunohistochemistry, Mesothelioma, Latency, Carcinogenesis.

Related studies

• Human T cell responses to endogenously presented HLA-A*0201 restricted peptides of Simian virus 40 large T antigen — M.P. Velders, M.F. Macedo, et al. (2001)
• Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue — C. Pepper, B. Jasani, et al. (1996)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• No implication of Simian virus 40 in pathogenesis of malignant pleural mesothelioma in Slovenia — J. Hmeljak, I. Kern, et al. (2010)
• The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas — A. De Luca, A. Baldi, et al. (1997)
• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)

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