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.

中文翻译：

---

猿猴病毒 40 (SV40) 在英国恶性胸膜间皮瘤中起作用吗？在对可能受影响的出生队列进行的敏感 RNA 原位杂交研究中没有发现任何作用

背景：在 1956 年至 1962 年期间，大约三分之一的英国接种脊髓灰质炎疫苗的人口意外接种了受猿猴病毒 40 (SV40) 污染的脊髓灰质炎疫苗。随后在实验和动物模型中证明 SV40 是一种致癌病毒。从那时起，SV40 致癌蛋白大 T 抗原（SV40 Tag）已被证明会导致石棉处理的人胸膜间皮细胞和石棉暴露 SV40 Tag 转基因小鼠恶性胸膜间皮瘤的恶性转化。本研究旨在调查 SV40 标签与暴露于石棉和 SV40 污染脊髓灰质炎疫苗组合峰值水平的英国人口出生队列中的人类恶性胸膜间皮瘤样本之间的可能关联。材料和方法：对从 8 年（1998 年至 2005 年）期间收集的 139 例胸膜间皮瘤病例的存档手术标本制备的肿瘤和背景肺组织微阵列进行了分析。这些代表的出生队列与 1950 年至 1960 年期间重叠，暴露于高水平的石棉和 SV40 污染的活脊髓灰质炎疫苗。在新型RNAscope技术的基础上，采用高灵敏度、特异的SV40 Tag RNA原位杂交检测方法研究SV40 Tag mRNA的表达。结果：尽管对包括的外部阳性和阴性对照获得了适当的结果，但在 127 个可评估的肿瘤病例中的任何一个中均未检测到 SV40 标签 RNA。结论：在这一大系列病例中完全没有 SV40 标签 mRNA 与实验证据相矛盾，这些证据表明 SV40 与英国人群中暴露于石棉的恶性胸膜间皮瘤有关。讨论了阴性结果的替代解释以排除可能的混杂因素。