Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts

Our plain-English summary of Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts, by F.S. Alchami, R.L. Attanoos, A. Gibbs, et al (Applied Immunohistochemistry & Molecular Morphology, 2020).

The study

• Authors: F.S. Alchami, R.L. Attanoos, A. Gibbs, F. Morgan, B. Jasani
• Journal: Applied Immunohistochemistry & Molecular Morphology
• Published: 2020;28(6):444-447
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines.

Materials And Methods: Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology.

Results: SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included.

Conclusion: The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.

In plain English

This laboratory study looked for simian virus 40 (SV40), an accidental contaminant of some polio vaccines, in UK malignant pleural mesothelioma tumors. The authors tested archived surgical tissue from 139 cases submitted in Cardiff, Wales, between 1998 and 2005. Patients were born between 1918 and 1981, spanning what the authors call the peak vaccine contamination period (1950 to 1960). The paper does not report individual exposure histories; the authors estimated about 80% were likely asbestos-exposed. Using a sensitive test (RNAscope) for the messenger RNA of the virus's large T antigen, 127 cases gave usable results. No SV40 signal appeared in any of 381 tumor cores or 127 background lung cores, while control cells gave expected results. The authors concluded the findings do not support a role for SV40 in the progression of UK pleural mesothelioma, but do not completely exclude a role in starting it. Possible explanations they listed included too little live, active SV40 received to act with asbestos, the large T antigen possibly becoming undetectable over the decades-long latency, few sarcomatoid tumors (12%), and test limits.

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 pathology study of archived surgical tumor tissue, using tissue microarrays tested by RNA in situ hybridization (RNAscope) for SV40 large T antigen mRNA
• Who was studied: 139 cases of malignant pleural mesothelioma submitted to Cardiff and Vale University Health Board (Wales, UK) between 1998 and 2005. Median age 65 (range 24 to 85) years, male to female ratio 9 to 1. Specimens from 1999 were not used.
• Exposure: Possible exposure to SV40 from contaminated polio vaccines, inferred from birth years (1918 to 1981, covering the 1950 to 1960 peak contamination period). The article does not report individual asbestos exposure histories and names no fiber types. The authors estimated that 80% of cases were likely asbestos-exposed.
• Main results:
  • Of the 139 cases, 127 gave adequate results. Excluded were 3 technical fails and 9 quality-control fails.
  • The positive control cells (Ori 3) and negative control cells (K2) stained as expected.
  • SV40 large T antigen RNA was not detected in any tumor core (0 of 381) or background lung core (0 of 127).
  • For the 28 tumor samples reported by the testing company (ACD), the authors' reading agreed 100% with the company's on quality control and SV40 results.
  • 17 tumors (12%) were of the sarcomatoid subtype and 86 (62%) were epithelioid.
• The authors' conclusion: The authors concluded that their negative findings do not support a role of SV40 in the progression of malignant pleural mesothelioma in the UK, though they do not completely exclude a role in the initiation of this tumor type. They added that the findings do not rule out a role in countries where contaminated vaccine use continued beyond 1962 or where SV40 infection is endemic.
• Limitations the authors state:
  • The estimate of combined asbestos and SV40 exposure rests on an assumption that these birth cohorts received sufficiently high doses of live SV40.
  • The authors note that UK contaminated batches were of the formaldehyde-inactivated Salk vaccine. The dose of live or oncogenically active SV40 the patients received may therefore have been below the threshold needed to act together with asbestos.
  • Given the long latency, SV40 might play only a transient role and leave tumor cells without any detectable large T antigen.
  • Only 12% of tumors were sarcomatoid, the type seen in the mouse model, which might have reduced the chance of detection.
  • The RNAscope method may not detect the rapidly degradable large T antigen mRNA made by the episomal form of SV40.

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, Carcinogenic, Malignant Transformation, Mesothelial Cells, Confounding.

Related studies

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• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)
• The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor — P. Cacciotti, L. Strizzi, et al. (2002)
• High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma — E. Mazzoni, A. Corallini, et al. (2012)
• Mesothelioma mortality in Europe: impact of asbestos consumption and simian virus 40 — K. Leithner, A. Leithner, et al. (2006)
• Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity — M. Bocchetta, I. Di Resta, et al. (2000)

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