Epstein–Barr virus in breast cancer: artefact or aetiological agent?

Murray, PG

doi:10.1002/path.2032

Cited by 17 publications

(5 citation statements)

References 19 publications

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“…Whereas EBV infection in certain tumour types has been firmly established by several independent research groups, its association with other tumour entities is still controversial 27 56…”

Section: Controversiesmentioning

confidence: 99%

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Epstein–Barr virus-associated tumours: an update for the attention of the working pathologist

et al. 2007

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Epstein–Barr virus (EBV) is a herpesvirus associated with approximately 1% of tumours worldwide. EBV is the epitome of B lymphotropic viruses, but the spectrum of tumours it is associated with extends to T lymphocyte and NK cell malignancies, various types of carcinomas and smooth muscle tumours. Ubiquitous EBV infection in humans implies that most individuals carry EBV-infected cells. Therefore, mere detection of the virus in individuals with a tumour is not sufficient for establishing a causal relationship between both events, but instead requires unequivocal detection of viral nucleic acids or viral proteins in the tumour cells. Recent controversies about EBV infection in several carcinomas mainly resulted from such technical issues. The gold standard remains in situ EBER detection, but detection of EBNA1 would be an interesting alternative. EBV detection can be helpful for diagnostic, prognostic and therapeutic purposes. The rate of EBV association with entities such as NK/T cell tumours of the nasal type is so high that absence of detection of the virus in such a lesion should cast doubt of the accuracy of the diagnosis. Similarly, diagnosis of EBV-associated follicular pseudo-tumour obviously requires detection of the virus. EBV-positive common gastric adenocarcinomas seem to have a better prognosis than their EBV-negative counterparts and identification of the virus in B cell lymphoproliferations in immunocompromised individuals will guide therapeutic options. In conclusion, EBV-associated tumours are common enough to be relevant for the pathologist in everyday practice, but there is a need to facilitate detection of the virus (eg EBNA1 antibody).

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“…Whereas EBV infection in certain tumour types has been firmly established by several independent research groups, its association with other tumour entities is still controversial 27 56…”

Section: Controversiesmentioning

confidence: 99%

“…Studies assessing EBV association with breast adenocarcinomas have reported contradictory results 56. This is probably at least partly related to the antibody directed against EBNA1 (clone 2B4).…”

Section: Controversiesmentioning

confidence: 99%

Epstein–Barr virus-associated tumours: an update for the attention of the working pathologist

et al. 2007

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“…Each of these viruses has known oncogenic potential and has been identified in normal and malignant human breast tissues. However, the identification of HPV, MMTV and EBV in breast tumours has been challenged [3]–[5]. The reasons for these challenges vary and include failure of some investigators to identify viral sequences in breast tumours and breast cancer cultured cell lines, concern about contamination of analyses based on polymerase chain reaction (PCR) techniques, and concern that outcomes based on immunohistochemistry may be non-specific and due to cross reacting proteins.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer

et al. 2012

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BackgroundThe purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers.Materials and MethodsAll the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc).ResultsEBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk – EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples.ConclusionsWe conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

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“…Others found that the higher expression of EBV was present in the medullary than the lobular carcinoma. [34] EBV tends to infect young persons of both sexes suggesting a genetic predisposition or early life exposure. It also affects older ages if the immune system is diminished.…”

Section: Published By Sciedu Pressmentioning

confidence: 99%

Immunohistochemical detection of human cytomegalovirus, Epstein-Barr virus and human papillomavirus in invasive breast carcinoma in Egyptian women: A tissue microarray study

Ahmed

Yussif

2016

JST

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Background and aim: Breast cancer is the commonest malignant tumor and a common cause of cancer death in women all over the world. Some recent studies attributed breast cancer to viral infection. This study aimed to evaluate the expression of HCMV, EBV and HPV in invasive carcinoma of the breast among the Egyptian women by immunohistochemistry and whether there is a relationship between the prognostic factors of breast carcinoma and these viruses. Patients and methods: This retrospective study included 107 selected cases of invasive breast carcinoma. Slides cut from tissue microarray prepared blocks were stained immunohistochemically for HCMV, EBV and HPV antigens. The association of such viruses with the clinicopathological features, tumor recurrence and patient death was evaluated statistically. Result: HCMV, EBV and HPV were present in 43.9%, 10.3% and 24.3% of cases respectively. HCMV was associated significantly with the tumor grade, mitotic count (P = .01), IDC, ER, PR, Her2/neu and molecular subtype (P = .032, .002, .02, .005, .003) respectively. EBV was associated with the tumor size, stage and histological type (P = . 025, .005, .009) respectively. HPV wasn't associated with any of the clinicopathological characteristics. None of these viruses was associated with the tumor recurrence or patient death. Conclusion: HCMV and EBV might be contributing factors for the development and behavioural alteration of breast carcinoma, representing potential tools for the detection of specific therapies for this cancer. Further studies on a larger number of cases using other techniques such as CISH for specific typing of the viruses especially HPV can add more information.

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Epstein–Barr virus in breast cancer: artefact or aetiological agent?

Cited by 17 publications

References 19 publications

Epstein–Barr virus-associated tumours: an update for the attention of the working pathologist

Epstein–Barr virus-associated tumours: an update for the attention of the working pathologist

Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer

Immunohistochemical detection of human cytomegalovirus, Epstein-Barr virus and human papillomavirus in invasive breast carcinoma in Egyptian women: A tissue microarray study

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