In situ detection of Epstein–Barr virus in non‐small cell lung carcinomas

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Abstract
Epstein–Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and lymphoepithelioma‐like carcinomas (LELC) of foregut‐derived organs. Recently this group of EBV‐associated carcinomas has been expanded by the identification of the virus in conventional adenocarcinomas of the stomach. In situ hybridization (ISH) using a sensitive digoxigenin‐labelled EBER RNA probe was performed on 167 consecutive unselected primary non‐small cell lung carcinomas, to determine the frequency of EBV association in these tumours. Nine cases (5·4 per cent) showed strong EBER signals in the tumour cell nuclei. By immunohistochemistry, 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 positive tumours were LELC, whereas no conventional type of non‐small cell lung carcinoma showed EBV association. The LELC presented a morphological spectrum from undifferentiated to squamoid or glandular differentiation. The patients showed a male to female ratio of 8:1. The mean age at presentation was 48 years. Smoking was not a risk factor. All patients were alive at follow‐up periods of 23–52 months. Southern blot analysis performed on eight of the nine positive tumours showed a clonal episomal form of EBV, suggesting the clonal expansion of an infected tumour cell early in oncogenesis. These characteristics of the EBV‐associated lung tumours justify their consideration as a distinct clinicopathological entity.