Mutations of p53 gene and SV40 sequences in asbestos associated and non-asbestos-associated mesotheliomas

Aim-To examine mesotheliomas for a possible relation between p53 immunostai ning, p53 gene mutation, simian virus 40 (SV40), and asbestos exposure. Methods-Paraffin sections from 11 mesotheliomas were used fbr p53 immunosta ining and also to extract DNA. This was analysed for the presence of mutati ons in exons 5 to 8 of the p53 gene using a "cold" single strand conformati onal polymorphism method, together with sequencing. The DNA from the paraff in sections was also used to search for SV40 sequences. A 105 base pair seg ment at the 3' of the SV40 large T antigen (Tag) was targeted and any PCR a mplification products were sequenced to confirm that they were of SV40 orig in. EDAX electron microscopic differential mineral fibre counts were perfor med on dried lung tissue at a specialist referral centre. Results-The fibre counts showed that seven of the mesotheliomas were associ ated with abnormally high asbestos exposure. Of these, two showed p53 immun ostaining, none showed p53 gene mutation, and five showed SV40. Of the four other mesotheliomas, three showed p53 immunostaining, one showed a (silent ) p53 mutation, and none showed SV40. The difference in frequency of SV40 d etection was significant at the p < 0.05 level. Conclusions-Immunostaining for the p53 gene was relatively common but p53 m utations were rare in this series. SV40 virus sequence was detected in five of seven asbestos associated mesotheliomas but in none of the non-asbestos -associated mesotheliomas. This suggests there may be a synergistic interac tion between asbestos and SV40 in human mesotheliomas. A study with a large r number of cases is needed to investigate these observations further.