Evidence against a role for simian virus 40 in malignant mesothelioma in Japan

Abstract

10040 Background: Malignant mesothelioma is a highly aggressive tumor arising from serosal membranes, most commonly the pleura. Worldwide incidence is increasing because of widespread exposure to asbestos, the major causal agent. Incidence of this disease also is increasing dramatically in Japan. Association of simian virus 40 (SV40) with malignant mesothelioma has been reported, suggesting that SV40 plays an important role in the origin of a subset of these tumors. Most recently, evidence against any role for SV40 in this disease has been also reported. The role of SV40 in malignant mesothelioma remains still controversial. In addition, it has been argued that differences in the reported frequency of SV40 detection in malignant mesothelioma may be related to geographic variation in populations exposed to the virus. Whether SV40 is associated with malignant mesothelioma in Japan therefore is an important issue. However, no study concerning SV40 in malignant mesothelioma has been reported from Japan. Methods: To address this, we studied 35 malignant mesotheliomas including 32 men and 3 women with a median age of 61 years (ranges 34 to 85) and examined the presence of SV40 large T antigen DNA with real time PCR based on TaqMan technology using primers that PCR amplified a specific 156-bp region of the large Tag of SV40 as well as its expression with immnohistological methods using anti-SV40 large T antigen antibody (pAb101, Santa Cruz Biotechnology, Inc., CA). Results: Two of 35 mesotheliomas were considered positive for the presence of SV40 large T antigen DNA, showing ratios of 36.0 and 4.9. The ratio in the positive control was 199.0. The two positive cases consisted of one epithelioid tumor and one biphasic tumor. In addition, none of 35 malignant mesothelioma specimens were positve for staining with SV40 large T antigen antibody; in contrast, diffuse staining for SV40 large T antigen was observed in the cytoplasm and on the cell membranes in the positive control. Conclusions: Taken together, these findings strongly argue against any role of SV40 in the etiology of the majority of malignant mesothelioma in Japan. No significant financial relationships to disclose.