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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

Alchami, Fouad S. MD, FRCpath*,†; Attanoos, Richard L. MD, FRCpath*; Gibbs, Allen MD*; Morgan, Fiona BSc*; Jasani, Bharat PhD, MBChB, FRCPath*,‡

Applied Immunohistochemistry & Molecular Morphology: June 12, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/PAI.0000000000000779
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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.

*Department of Cellular Pathology, University Hospital of Wales, Cardiff, Wales

Department of Anatomical Pathology, Sidra Medicine, Doha, Qatar

Targos Molecular Pathology GmbH, Kassel, Germany

Supported by Environmental Lung Disease Research Group, Cardiff University, Wales.

R.L.A. and A.G. undertake expert testimony work which is used in asbestos-related litigation for both claimants and defendants. This study is non-commissioned. The remaining authors declare no conflict of interest.

Reprints: Fouad S. Alchami, MD, FRCpath, Department of Anatomical Pathology, Sidra Medicine, Doha 26999, Qatar (e-mail: falchami@sidra.org).

Received January 24, 2019

Accepted April 18, 2019

Copyright 2019 Wolters Kluwer Health, Inc. All rights reserved.