IN-SITU DETECTION OF EPSTEIN-BARR-VIRUS IN NON-SMALL-CELL LUNG CARCINOMAS

Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal ca rcinoma and lymphoepithelioma-like carcinomas (LELC) of foregut-derive d organs. Recently this group of EBV-associated carcinomas has been ex panded by the identification of the virus in conventional adenocarcino mas of the stomach. In situ hybridization (ISH) using a sensitive digo xigenin-labelled EBER RNA probe was performed on 167 consecutive unsel ected primary non-small cell lung carcinomas, to determine the frequen cy of EBV association in these tumours. Nine cases (5.4 per cent) show ed strong EBER signals in the tumour cell nuclei. By immunohistochemis try, four of the EBER-positive tumours showed patchy expression of the viral latent membrane protein (LMP-1) and none showed any expression of the EBV nuclear antigen 2 (EBNA2). Morphologically, all the positiv e tumours were LELC, whereas no conventional type of non-small cell lu ng carcinoma showed EBV association. The LELC presented a morphologica l spectrum from undifferentiated to squamoid or glandular differentiat ion. The patients showed a male to female ratio of 8:1. The mean age a t presentation was 48 years. Smoking was not a risk factor. All patien ts were alive at follow-up periods of 23-52 months. Southern blot anal ysis performed on eight of the nine positive tumours showed a clonal e pisomal form of EBV, suggesting the clonal expansion of an infected tu mour cell early in oncogenesis. These characteristics of the EBV-assoc iated lung tumours justify their consideration as a distinct clinicopa thological entity.