Skip to main content
Top
Published in: Breast Cancer Research 1/2002

Open Access 01-02-2002 | Research article

Lack of evidence for an association of Epstein–Barr virus infection with breast carcinoma

Authors: Kathrin Herrmann, Gerald Niedobitek

Published in: Breast Cancer Research | Issue 1/2002

Login to get access

Abstract

Background

Epstein–Barr virus (EBV) is a ubiquitous human γ-herpes virus infecting more than 90% of the population worldwide. EBV is associated with certain malignancies (e.g. Burkitt lymphoma, Hodgkin lymphoma and nasopharyngeal carcinoma). Recent studies have raised the possibility that EBV may also be involved in the pathogenesis of breast carcinoma, the most common carcinoma of females. If substantiated, this finding would have major implications regarding prevention and therapy of the disease. The studies published so far have employed diverse methods, however, and the results have been controversial.

Methods

Using the EBV DNA PCR, EBV DNA in situ hybridisation and in situ hybridisation for the detection of the EBV-encoded RNAs, and using immunohistochemistry for the demonstration of the EBV-encoded nuclear antigen 1, we have studied a series of 59 invasive breast carcinomas for evidence of EBV infection.

Results

EBV-encoded RNA-specific in situ hybridisation and EBV-encoded nuclear antigen 1 immunohistochemistry were negative in all cases. Using the PCR, EBV DNA was detected in four out of 59 cases. These cases were further studied by EBV DNA in situ hybridisation, showing an absence of viral DNA from the tumour cells.

Conclusion

These results indicate that breast carcinoma is not an EBV-associated tumour.
Literature
1.
go back to reference International Agency for Research on Cancer: Epstein–Barr Virus and Kaposi's Sarcoma Herpesvirus/Human Herpesvirus 8. Lyon: World Health Organisation. 1997 International Agency for Research on Cancer: Epstein–Barr Virus and Kaposi's Sarcoma Herpesvirus/Human Herpesvirus 8. Lyon: World Health Organisation. 1997
2.
go back to reference Labrecque LG, Barnes DM, Fentiman IS, Griffin BE: Epstein–Barr virus in epithelial cell tumors: a breast cancer study. Cancer Res. 1995, 55: 39-45.PubMed Labrecque LG, Barnes DM, Fentiman IS, Griffin BE: Epstein–Barr virus in epithelial cell tumors: a breast cancer study. Cancer Res. 1995, 55: 39-45.PubMed
3.
go back to reference Bonnet M, Guinebretiere J-M, Kremmer E, Grunewald V, Benhamou E, Contesso G, Joab I: Detection of Epstein–Barr virus in invasive breast cancers. J Natl Cancer Inst. 1999, 91: 1376-1381. 10.1093/jnci/91.16.1376.CrossRefPubMed Bonnet M, Guinebretiere J-M, Kremmer E, Grunewald V, Benhamou E, Contesso G, Joab I: Detection of Epstein–Barr virus in invasive breast cancers. J Natl Cancer Inst. 1999, 91: 1376-1381. 10.1093/jnci/91.16.1376.CrossRefPubMed
4.
go back to reference Ambinder RF, Robertson KD, Moore SM, Yang J: Epstein–Barr virus as a therapeutic target in Hodgkin's disease and nasopharyngeal carcinoma. Semin Cancer Biol. 1996, 7: 217-226. 10.1006/scbi.1996.0029.CrossRefPubMed Ambinder RF, Robertson KD, Moore SM, Yang J: Epstein–Barr virus as a therapeutic target in Hodgkin's disease and nasopharyngeal carcinoma. Semin Cancer Biol. 1996, 7: 217-226. 10.1006/scbi.1996.0029.CrossRefPubMed
5.
go back to reference Sing AP, Ambinder RF, Hong DJ, Jensen M, Batten W, Petersdorf E, Greenberg PD: Isolation of Epstein–Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed–Sternberg cells: implications for immune-mediated therapy of EBV+ Hodgkin's disease. Blood. 1997, 89: 1978-1986.PubMed Sing AP, Ambinder RF, Hong DJ, Jensen M, Batten W, Petersdorf E, Greenberg PD: Isolation of Epstein–Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed–Sternberg cells: implications for immune-mediated therapy of EBV+ Hodgkin's disease. Blood. 1997, 89: 1978-1986.PubMed
6.
go back to reference Roskrow MA, Suzuki N, Gan Y-j, Sixbey JW, Ng CYC, Kimbrough S, Hudson M, Brenner MK, Heslop HE, Rooney CM: Epstein–Barr virus (EBV)-specific cytotoxic lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin's disease. Blood. 1998, 91: 2925-2934.PubMed Roskrow MA, Suzuki N, Gan Y-j, Sixbey JW, Ng CYC, Kimbrough S, Hudson M, Brenner MK, Heslop HE, Rooney CM: Epstein–Barr virus (EBV)-specific cytotoxic lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin's disease. Blood. 1998, 91: 2925-2934.PubMed
7.
go back to reference Niedobitek G, Hansmann ML, Herbst H, Young LS, Dienemann D, Hartmann CA, Finn T, Pitteroff S, Welt A, Anagnostopoulos I, Friedrich R, Lobeck H, Sam CK, Araujo I, Rickinson AB, Stein H: Epstein–Barr virus and carcinomas: undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus. J Pathol. 1991, 165: 17-24.CrossRefPubMed Niedobitek G, Hansmann ML, Herbst H, Young LS, Dienemann D, Hartmann CA, Finn T, Pitteroff S, Welt A, Anagnostopoulos I, Friedrich R, Lobeck H, Sam CK, Araujo I, Rickinson AB, Stein H: Epstein–Barr virus and carcinomas: undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus. J Pathol. 1991, 165: 17-24.CrossRefPubMed
8.
go back to reference Lespagnard L, Cochaux P, Larsimont D, Degeyter M, Velu T, Heimann R: Absence of Epstein–Barr virus in medullary carcinoma of the breast as demonstrated by immunophenotyping, in situ hybridization and polymerase chain reaction. Am J Clin Pathol. 1995, 103: 449-452.CrossRefPubMed Lespagnard L, Cochaux P, Larsimont D, Degeyter M, Velu T, Heimann R: Absence of Epstein–Barr virus in medullary carcinoma of the breast as demonstrated by immunophenotyping, in situ hybridization and polymerase chain reaction. Am J Clin Pathol. 1995, 103: 449-452.CrossRefPubMed
9.
go back to reference Dadmanesh F, Peterse JL, Sapino A, Fonelli A, Eusebi V: Lymphoepithelioma-like carcinoma of the breast: lack of evidence of Epstein–Barr virus infection. Histopathology. 2001, 38: 54-61. 10.1046/j.1365-2559.2001.01055.x.CrossRefPubMed Dadmanesh F, Peterse JL, Sapino A, Fonelli A, Eusebi V: Lymphoepithelioma-like carcinoma of the breast: lack of evidence of Epstein–Barr virus infection. Histopathology. 2001, 38: 54-61. 10.1046/j.1365-2559.2001.01055.x.CrossRefPubMed
10.
go back to reference Luqmani YA, Shousha S: Presence of Epstein–Barr virus in breast carcinoma. Int J Oncol. 1995, 6: 899-903.PubMed Luqmani YA, Shousha S: Presence of Epstein–Barr virus in breast carcinoma. Int J Oncol. 1995, 6: 899-903.PubMed
11.
go back to reference Chu PG, Chang KL, Chen Y-Y, Weiss LM: No significant association of Epstein–Barr virus infection with invasive breast caricnoma. Am J Pathol. 2001, 159: 571-578.CrossRefPubMedPubMedCentral Chu PG, Chang KL, Chen Y-Y, Weiss LM: No significant association of Epstein–Barr virus infection with invasive breast caricnoma. Am J Pathol. 2001, 159: 571-578.CrossRefPubMedPubMedCentral
12.
go back to reference Fina F, Romain S, Ouafik L, Palmari J, Ben Ayed F, Benharkat S, Bonnier P, Spyratos F, Foekens JA, Rose C, Buisson M, Gerard H, Reymond MO, Seigneurin JM, Martin PM: Frequency and genome load of Epstein–Barr virus in 509 breast cancers from different geographic areas. Br J Cancer. 2001, 84: 783-790. 10.1054/bjoc.2000.1672.CrossRefPubMedPubMedCentral Fina F, Romain S, Ouafik L, Palmari J, Ben Ayed F, Benharkat S, Bonnier P, Spyratos F, Foekens JA, Rose C, Buisson M, Gerard H, Reymond MO, Seigneurin JM, Martin PM: Frequency and genome load of Epstein–Barr virus in 509 breast cancers from different geographic areas. Br J Cancer. 2001, 84: 783-790. 10.1054/bjoc.2000.1672.CrossRefPubMedPubMedCentral
13.
go back to reference McCall SA, Lichy JH, Bijwaard KE, Aguilera NS, Chu W-S, Taubenberger JK: Epstein–Barr virus detection in ductal carcinoma of the breast. J Natl Cancer Inst. 2001, 93: 148-150. 10.1093/jnci/93.2.148.CrossRefPubMed McCall SA, Lichy JH, Bijwaard KE, Aguilera NS, Chu W-S, Taubenberger JK: Epstein–Barr virus detection in ductal carcinoma of the breast. J Natl Cancer Inst. 2001, 93: 148-150. 10.1093/jnci/93.2.148.CrossRefPubMed
14.
go back to reference Glaser SL, Ambinder RF, DiGuiseppe JA, Horn-Ross PL, Hsu JL: Absence of Epstein–Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers. Int J Cancer. 1998, 75: 555-558. 10.1002/(SICI)1097-0215(19980209)75:4<555::AID-IJC10>3.3.CO;2-2.CrossRefPubMed Glaser SL, Ambinder RF, DiGuiseppe JA, Horn-Ross PL, Hsu JL: Absence of Epstein–Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers. Int J Cancer. 1998, 75: 555-558. 10.1002/(SICI)1097-0215(19980209)75:4<555::AID-IJC10>3.3.CO;2-2.CrossRefPubMed
15.
go back to reference Chu JS, Chen CC, Chang KJ: In situ detection of Epstein–Barr virus in breast cancer. Cancer Lett. 1998, 124: 53-57. 10.1016/S0304-3835(97)00449-7.CrossRefPubMed Chu JS, Chen CC, Chang KJ: In situ detection of Epstein–Barr virus in breast cancer. Cancer Lett. 1998, 124: 53-57. 10.1016/S0304-3835(97)00449-7.CrossRefPubMed
16.
go back to reference Grinstein S, Preciado MV, Gattuso P, Chabay PA, Warren WH, De Matteo E, Gould VE: Demonstration of Epstein–Barr virus in carcinomas of various sites. Cancer Res. 2002, 62: 4876-4878.PubMed Grinstein S, Preciado MV, Gattuso P, Chabay PA, Warren WH, De Matteo E, Gould VE: Demonstration of Epstein–Barr virus in carcinomas of various sites. Cancer Res. 2002, 62: 4876-4878.PubMed
17.
go back to reference Raab-Traub N, Flynn K: The structure of the termini of the Epstein–Barr virus as a marker of clonal cellular proliferation. Cell. 1986, 47: 883-889.CrossRefPubMed Raab-Traub N, Flynn K: The structure of the termini of the Epstein–Barr virus as a marker of clonal cellular proliferation. Cell. 1986, 47: 883-889.CrossRefPubMed
18.
go back to reference Grässer FA, Murray PG, Kremmer E, Klein K, Remberger K, Feiden W, Reynolds G, Niedobitek G, Young LS, Mueller-Lantzsch N: Monoclonal antibodies directed against the Epstein–Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin's disease. Blood. 1994, 84: 3792-3798.PubMed Grässer FA, Murray PG, Kremmer E, Klein K, Remberger K, Feiden W, Reynolds G, Niedobitek G, Young LS, Mueller-Lantzsch N: Monoclonal antibodies directed against the Epstein–Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin's disease. Blood. 1994, 84: 3792-3798.PubMed
19.
go back to reference Murray PG, Niedobitek G, Kremmer E, Grasser F, Reynolds GM, Cruchley A, Williams DM, Muller-Lantzsch N, Young LS: In situ detection of the Epstein–Barr virus-encoded nuclear antigen 1 in oral hairy leukoplakia and virus-associated carcinomas. J Pathol. 1996, 178: 44-47. 10.1002/(SICI)1096-9896(199601)178:1<44::AID-PATH471>3.0.CO;2-0.CrossRefPubMed Murray PG, Niedobitek G, Kremmer E, Grasser F, Reynolds GM, Cruchley A, Williams DM, Muller-Lantzsch N, Young LS: In situ detection of the Epstein–Barr virus-encoded nuclear antigen 1 in oral hairy leukoplakia and virus-associated carcinomas. J Pathol. 1996, 178: 44-47. 10.1002/(SICI)1096-9896(199601)178:1<44::AID-PATH471>3.0.CO;2-0.CrossRefPubMed
20.
go back to reference Sugawara Y, Mizugaki Y, Uchida T, Torii T, Imai S, Makuuchi M, Takada K: Detection of Epstein–Barr virus (EBV) in hepatocellular carcinoma tissue: a novel EBV latency characterized by the absence of EBV-encoded small RNA expression. Virology. 1999, 256: 196-202. 10.1006/viro.1999.9619.CrossRefPubMed Sugawara Y, Mizugaki Y, Uchida T, Torii T, Imai S, Makuuchi M, Takada K: Detection of Epstein–Barr virus (EBV) in hepatocellular carcinoma tissue: a novel EBV latency characterized by the absence of EBV-encoded small RNA expression. Virology. 1999, 256: 196-202. 10.1006/viro.1999.9619.CrossRefPubMed
21.
go back to reference Niedobitek G, Young LS, Lau R, Brooks L, Greenspan D, Greenspan JS, Rickinson AB: Epstein–Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase. J Gen Virol. 1991, 72: 3035-3046.CrossRefPubMed Niedobitek G, Young LS, Lau R, Brooks L, Greenspan D, Greenspan JS, Rickinson AB: Epstein–Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase. J Gen Virol. 1991, 72: 3035-3046.CrossRefPubMed
22.
go back to reference Niedobitek G, Herbst H: In situ detection of Epstein–Barr virus DNA and of viral gene products. In Epstein–Barr Virus Protocols. Edited by: Wilson JB, May GHW. 2001, Totowa, NJ: Humana Press, 79-91.CrossRef Niedobitek G, Herbst H: In situ detection of Epstein–Barr virus DNA and of viral gene products. In Epstein–Barr Virus Protocols. Edited by: Wilson JB, May GHW. 2001, Totowa, NJ: Humana Press, 79-91.CrossRef
23.
go back to reference Yates J, Waren N, Reisman D, Sugden B: A cis-acting element from the Epstein–Barr virus genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci USA. 1984, 81: 3806-3810.CrossRefPubMedPubMedCentral Yates J, Waren N, Reisman D, Sugden B: A cis-acting element from the Epstein–Barr virus genome that permits stable replication of recombinant plasmids in latently infected cells. Proc Natl Acad Sci USA. 1984, 81: 3806-3810.CrossRefPubMedPubMedCentral
24.
go back to reference Nicholls JM, Agathanggelou A, Fung K, Xianggou Z, Niedobitek G: The association of squamous cell carcinomas of the nasopharynx with Epstein–Barr virus shows geographic variation reminiscent of Burkitt's lymphoma. J Pathol. 1997, 183: 164-168. 10.1002/(SICI)1096-9896(199710)183:2<164::AID-PATH919>3.3.CO;2-A.CrossRefPubMed Nicholls JM, Agathanggelou A, Fung K, Xianggou Z, Niedobitek G: The association of squamous cell carcinomas of the nasopharynx with Epstein–Barr virus shows geographic variation reminiscent of Burkitt's lymphoma. J Pathol. 1997, 183: 164-168. 10.1002/(SICI)1096-9896(199710)183:2<164::AID-PATH919>3.3.CO;2-A.CrossRefPubMed
Metadata
Title
Lack of evidence for an association of Epstein–Barr virus infection with breast carcinoma
Authors
Kathrin Herrmann
Gerald Niedobitek
Publication date
01-02-2002
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2002
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr561

Other articles of this Issue 1/2002

Breast Cancer Research 1/2002 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine