Detection of the Epstein-Barr virus in primary adenocarcinoma of the lung with Signet-Ring cells

Abstract

The Epstein-Barr virus (EBV) is directly implicated in the pathogenesis of a variety of undifferentiated carcinomas and has also been identified in conventional adenocarcinomas of the stomach. To date, the association of EBV with non-small cell lung carcinoma is restricted to Asian patients. To evaluate the presence of EBV in lung cancers from Europeans, we investigated primary lung adenocarcinomas with a similar morphological tumour pattern to those of the stomach, specifically rare tumours with components of signet-ring cells. Three tumours of signet-ring cell type were examined by means of polymerase chain reaction (PCR). To localise the virus to the neoplastic cells, in situ hybridisation (ISH) was performed using an antisense Epstein-Barr virus encoded RNA probe. Immunohistochemistry was performed to evaluate the expression of latent membrane protein-1 (LMP-1) and EBV nuclear antigen 2 (EBNA-2). PCR investigation confirmed the presence of EBV in one case. Positive signals confined to tumour cells were present on ISH. None of the tumours showed expression of LMP-1 and EBNA-2. To our knowledge, this is the first report on the presence of EBV in primary adenocarcinoma of the lung in a Caucasian patient. The present study indicates that EBV may infect some lung cancers with a specific tumour pattern.

Epstein–Barr virus-associated adenocarcinomas and squamous-cell lung carcinomas

“…13,12 However, the neoplastic cells had an extremely low 7 LMP1 expression, and in situ hybridization for EBV early RNA (EBER) and clonal episomal EBV sequences have been demonstrated in tumour tissue, but only in Asian 9,23,12,25,26 and in two caucasic patients. 18,19 We agree with these data because our five cases of pure lymphoepitheliomalike carcinomas have been negative for EBV.…”

“…16 Only two pulmonary-carcinoma EBV associated in Caucasian patients have been recently reported. 18,19 Otherwise, several cases of lymphocyte rich adenocarcinomas but without EBV association have been also reported. 27,15 We describe 12 lung carcinomas (4 squamous-cell carcinomas and 8 adenocarcinomas) in an occidental population, all of them with EBV sequences in tumoral tissue demonstrated by PCR and/or EBER.…”

“…18,19 In consequence, it seems that EBV-associated lung carcinomas different to the typical lymphoepithelioma-like type could exist. 17,16 Our aim is to describe a series of pulmonary adenocarcinomas and squamous-cell carcinomas found in a 12-year period, characterized by a dense lymphoid stroma in an occidental population, and to demonstrate the presence of EBV in this kind of carcinomas.…”

Epstein–Barr virus plays no role in the tumorigenesis of small-cell carcinoma of the lung

“…12 We studied Epstein-Barr virus RNA in 78 cases of pulmonary nonlymphoepitheliomalike carcinoma using in situ hybridization methodology in 1992, and found none of them to be positive for Epstein-Barr virus. 15 In contrast, several recent studies reported that Epstein-Barr virus gene products were detected in pulmonary nonlymphoepithelioma-like carcinoma, such as pulmonary squamous cell carcinoma and neuroendocrine carcinoma 13 and small-cell carcinoma of the lung.…”

“…In contrast, there are few reports demonstrating EpsteinBarr virus infection in pulmonary carcinoma in Western populations. Huber et al 12 reported a case of pulmonary adenocarcinoma with signet-ring-cell features harboring Epstein-Barr virus by EBER-1 in situ hybridization and BamHI W region polymerase chain reaction methods. Using Epstein-Barr virus nuclear antigen-1 immunohistochemistry, Grinstein et al 13 recently found that two of the 22 cases of pulmonary squamous-cell carcinoma and two of the 10 cases of pulmonary neuroendocrine carcinoma were positive for Epstein-Barr virus.…”