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

Cerilli, Lisa A.; Chen, Yuanyuan; Mills, Stacey E.; Weiss, Lawrence M.

doi:10.1038/modpathol.3800024

Cited by 18 publications

(20 citation statements)

References 27 publications

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“…Two previous serologic studies found a higher seroprevalence of several EBV antibodies in lung cancer cases compared with healthy controls (Desgranges and de-The, 1979; Roy et al , 1994). Among tissue-based studies, some studies have found 5–10% positivity by EBER ISH or EBV nuclear antigen IHC (Kasai et al , 1994; Wong et al , 1995; Grinstein et al , 2002), whereas others have found no positivity by EBER ISH (Conway et al , 1996; Kijima et al , 2001; Hayakawa et al , 2003; Chu et al , 2004; Lim et al , 2009) and generally low or no positivity by other markers (Chu et al , 2004). Although EBER ISH is considered the gold standard for detecting EBV-associated cancers because of its high abundance in latently EBV-infected cells, it is not a perfect measure (Delecluse et al , 2007).…”

Section: Discussionmentioning

confidence: 99%

“…It has also been implicated in ∼10% of gastric cancers (Young and Rickinson, 2004). Although lung cancer cases in serological studies had higher EBV seropositivity than healthy controls (Desgranges and de-The, 1979; Roy et al , 1994), previous studies of EBV in lung tumour tissue have generally produced negative results, except in rare cases of lymphoepithelioma-like carcinomas (LELCs) (Chu et al , 2004; Lim et al , 2009). However, previous studies largely tested for expression of EBV-encoded small RNA ( EBER ), which is generally abundantly expressed in cells with latent EBV infection but occasionally may be absent or heterogeneously expressed in EBV DNA-positive tumours (Iwakiri and Takada, 2010).…”

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confidence: 99%

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Epstein–Barr virus microRNAs and lung cancer

et al. 2011

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Background:We conducted the first analysis of viral microRNAs (miRNAs) in lung cancer, with a focus on Epstein–Barr virus (EBV).Methods:We evaluated viral miRs with a two-channel oligo-array targeting mature, anti-sense miRNAs in 290 cases. In 48 cases, we compared microarray and real-time quantitative PCR (qPCR) expression for three EBV miRNAs. We tested for EBV DNA, RNA, and protein in tumour tissue from six cases with and six cases without strong qPCR-based evidence of EBV miRNAs.Results:The EBV miRNAs strongly differentiated between adenocarcinoma and squamous cell carcinoma using the microarray (P<0.01 for 9 out of 16 EBV miRNAs). However, microarray and qPCR measurements of BART1, BART2, and BHRF1–3 expression were not significantly correlated (P=0.53, 0.94, and 0.47, respectively). Although qPCR provided substantial evidence of EBV miRNAs in 7 out of 48 cases, only 1 of these 7 cases had detectable EBV DNA in tumour tissue. None had detectable EBV RNA or protein by histochemical stains.Conclusion:In a comprehensive evaluation of EBV miRNA, DNA, RNA, and protein in lung cancer, we found little evidence of EBV in lung tumour tissue. Discrepancies between microarray- and qPCR-based strategies highlight the difficulty of validating molecular markers of disease. Our results do not support a role of EBV in lung cancer.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Epstein–Barr virus microRNAs and lung cancer

et al. 2011

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“…A slightly higher frequency of EBER has been described in squamous cell carcinoma and neuroendocrine carcinomas (38). A subsequent study in small cell lung cancer however showed complete absence of EBER-1 by in situ hybridization (39) and no staining for ZEBRA and LMP-1 and only focal expression of EBNA-1. EBV was similarly absent in mesotheliomas and lung adenocarcinomas in the study by Conway et al (40).…”

Section: %) --------------------------------------------------------mentioning

confidence: 99%

Assessment of human papillomavirus and Epstein-Barr virus in lung adenocarcinoma

Lim

2009

Oncol Rep

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Abstract. The association of human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection with non-small cell lung cancer is controversial. HPV and EBV prevalence in a uniform population of lung adenocarcinoma was investigated, hypothesizing that there would be differences seen between smokers and non-smokers and between sexes. Patients involved in this study were selected from a single institution database of lung cancer. In total 497 patients with adenocarcinoma were identified and 110 patients had sufficient tissue for analysis with an in situ hybridization method that probed for high-risk and low-risk HPV and EBV. There were 65 males and 45 females, 78 patients with stage I-IIIA disease and 32 patients with stage IIIB-IV disease. There were similar number of smokers and non-smokers. Across all stages HPV and EBV staining was absent from all tissues examined. It is unlikely that HPV or EBV is an important etiological agent in adenocarcinoma of the lung, even among the neversmokers. IntroductionCigarette smoke is strongly associated with the development of lung cancer (1). While the epidemic of smoking has reduced through public health awareness programs and education, the incidence of lung cancer remains unabated. There has been a demographic change in the global pandemic with a global realignment of histological subtypes. Adenocarcinoma incidence is rising globally among both smokers and nonsmokers. Up to 30% of all diagnosed non-small cell lung cancer (NSCLC) among various Asian countries, including Singapore, do not have a history of exposure to cigarette smoking. These patients tend to be predominantly female and have adenocarcinoma (2). This has given rise to different postulates as to the possible etiologies of NSCLC in this distinct of patients, ranging from exposure to cooking oil fumes (3,4), as well as diet and cancer susceptibility genotypes among Asians (5-7). Human papillomavirus (HPV) and Epstein-Barr virus (EBV) have been variously described to be associated and causative with several cancers. HPV is likely to be causal in cervical carcinoma and head and neck squamous cell carcinoma (HNSCC), and EBV in nasopharyngeal carcinoma. There have been various reports of association between HPV and EBV with lung cancer but results have not been conclusive (8). Leveraging on the excess of non-tobacco related lung cancer in our patients we investigated HPV and EBV prevalence in a uniform population of adenocarcinoma of the lung, hypothesizing that there would be differences seen between smokers and nonsmokers and between sexes. Patients and methodsPatients. Patients involved in this study were selected from a database of NSCLC patients, diagnosed in a single institution (SGH) from 1999 to 2002. The study had the approval of the Institutional Review Board of National Cancer Centre Singapore. The main selection criterion was a diagnosis of adenocarcinoma. Four hundred and ninety-seven patients were identified and among them, 110 patients had sufficient tissue blocks available for our analysis using in ...

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“…Despite being associated with lymphoepithelioma-like carcinoma in the lung, mainly in Asian patients,27 different publications have failed to correlate EBV as a risk factor in the Western population. Koshiol et al 28 recently reported an evaluation of EBV miRNA, DNA, RNA and protein in adenocarcinoma and squamous cell lung carcinoma cases from Caucasian patients, showing little evidence of EBV in lung tumour.A lack of association has also been proposed in the tumourigenesis of small cell lung carcinoma 29…”

Section: Discussionmentioning

confidence: 99%