Skip to main content

Advertisement

SpringerLink
Log in

Epstein–Barr virus is seldom found in mammary epithelium of breast cancer tissue using in situ molecular methods

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Epstein–Barr virus (EBV) has been proposed as a possible etiological agent of breast cancer based on 21 reports of EBV in malignant breast tissues. Most of these studies used standard and nested solution polymerase chain reaction (PCR) techniques, both disadvantaged by susceptibility to contamination from laboratory EBV, and the inability to localize the signal to a specific cell type. To avoid these issues, we used in situ molecular methods of viral detection to reassess the frequency of EBV in malignant breast tissue. We used a commercial in situ hybridization (ISH) system with an EBER genome target, and a non-commercial in situ PCR (IS-PCR) method using primers specific for the BamH1 region. The assays were performed on malignant breast tissue sections from 70 breast cancer patients at the M. D. Anderson Cancer Center, Houston, TX. EBV was found in mammary epithelial cells, the cell type from which most breast cancers arise, in 2/70 (2.9%) of specimens using IS-PCR and in none of the specimens using ISH. Based on these findings that EBV was present in human mammary epithelial cells so infrequently, it is unlikely to play a causative role in most types of breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lespagnard L, Cochaux P, Larsimont D, Degeyter M, Velu T, Heimann R (1995) 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 103(4):449–452

    PubMed  CAS  Google Scholar 

  2. Bonnet M, Guinebretiere JM, Kremmer E, Grunewald V, Benhamou E, Contesso G, Joab I (1999) Detection of Epstein–Barr virus in invasive breast cancers. J Natl Cancer Inst 91(16):1376–1381

    Article  PubMed  CAS  Google Scholar 

  3. Brink AA, van Den Brule AJ, van Diest P, Meijer CJ (2000) Re: detection of Epstein–Barr virus in invasive breast cancers. J Natl Cancer Inst 92(8):655–656 author reply 656

    Article  PubMed  CAS  Google Scholar 

  4. Chu JS, Chen CC, Chang KJ (1998) In situ detection of Epstein–Barr virus in breast cancer. Cancer Lett 124(1):53–57

    Article  PubMed  CAS  Google Scholar 

  5. Chu PG, Chang KL, Chen YY, Chen WG, Weiss LM (2001) No significant association of Epstein–Barr virus infection with invasive breast carcinoma. Am J Pathol 159(2):571–578

    Article  PubMed  CAS  Google Scholar 

  6. Deshpande CG, Badve S, Kidwai N, Longnecker R (2002) Lack of expression of the Epstein–Barr virus (EBV) gene products, EBERs, EBNA1, LMP1, and LMP2A in breast cancer cells. Lab Invest 82(9):1193–1199

    PubMed  CAS  Google Scholar 

  7. Grinstein S, Preciado MV, Gattuso P, Chabay PA, Warren WH, De Matteo E, Gould VE (2002) Demonstration of Epstein–Barr virus in carcinomas of various sites. Cancer Res 62(17):4876–4878

    PubMed  CAS  Google Scholar 

  8. Herrmann K, Niedobitek G (2003) Lack of evidence for an association of Epstein–Barr virus infection with breast carcinoma. Breast Cancer Res 5(1):R13–R17

    Article  PubMed  CAS  Google Scholar 

  9. Kadivar M, Monabati A, Joulaee A, Hosseini N (2011) Epstein–Barr virus and breast cancer: lack of evidence for an association in Iranian women. Pathol Oncol Res. doi:10.1007/s12253-010-9325-z

  10. McCall SA, Lichy JH, Bijwaard KE, Aguilera NS, Chu WS, Taubenberger JK (2001) Epstein–Barr virus detection in ductal carcinoma of the breast. J Natl Cancer Inst 93(2):148–150

    Article  PubMed  CAS  Google Scholar 

  11. Murray PG, Lissauer D, Junying J, Davies G, Moore S, Bell A, Timms J, Rowlands D, McConkey C, Reynolds GM, Ghataura S, England D, Caroll R, Young LS (2003) Reactivity with A monoclonal antibody to Epstein–Barr virus (EBV) nuclear antigen 1 defines a subset of aggressive breast cancers in the absence of the EBV genome. Cancer Res 63(9):2338–2343

    PubMed  CAS  Google Scholar 

  12. Preciado MV, Chabay PA, De Matteo EN, Gonzalez P, Grinstein S, Actis A, Gass HD (2005) Epstein–Barr virus in breast carcinoma in Argentina. Arch Pathol Lab Med 129(3):377–381. doi:10.1043/1543-2165(2005)129<377:EVIBCI>2.0.CO;2

    PubMed  Google Scholar 

  13. Ribeiro-Silva A, Ramalho LN, Garcia SB, Zucoloto S (2004) Does the correlation between EBNA-1 and p63 expression in breast carcinomas provide a clue to tumorigenesis in Epstein–Barr virus-related breast malignancies? Braz J Med Biol Res 37(1):89–95

    Article  PubMed  CAS  Google Scholar 

  14. Thorne LB, Ryan JL, Elmore SH, Glaser SL, Gulley ML (2005) Real-time PCR measures Epstein–Barr virus DNA in archival breast adenocarcinomas. Diagn Mol Pathol 14(1):29–33

    Article  PubMed  CAS  Google Scholar 

  15. Trabelsi A, Rammeh S, Stita W, Mokni M, Mourou A, Korbi S (2008) Detection of Epstein–Barr virus in breast cancers with lymphoid stroma. Ann Biol Clin (Paris) 66(1):59–62

    CAS  Google Scholar 

  16. Arbach H, Viglasky V, Lefeu F, Guinebretiere JM, Ramirez V, Bride N, Boualaga N, Bauchet T, Peyrat JP, Mathieu MC, Mourah S, Podgorniak MP, Seignerin JM, Takada K, Joab I (2006) Epstein–Barr virus (EBV) genome and expression in breast cancer tissue: effect of EBV infection of breast cancer cells on resistance to paclitaxel (Taxol). J Virol 80(2):845–853. doi:10.1128/JVI.80.2.845-853.2006

    Article  PubMed  CAS  Google Scholar 

  17. Dadmanesh F, Peterse JL, Sapino A, Fonelli A, Eusebi V (2001) Lymphoepithelioma-like carcinoma of the breast: lack of evidence of Epstein–Barr virus infection. Histopathology 38(1):54–61

    Article  PubMed  CAS  Google Scholar 

  18. Fawzy S, Sallam M, Awad NM (2008) Detection of Epstein–Barr virus in breast carcinoma in Egyptian women. Clin Biochem 41(7–8):486–492

    Article  PubMed  CAS  Google Scholar 

  19. 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 (2001) Frequency and genome load of Epstein–Barr virus in 509 breast cancers from different geographical areas. Br J Cancer 84(6):783–790

    Article  PubMed  CAS  Google Scholar 

  20. Gaffey MJ, Frierson HF Jr, Mills SE, Boyd JC, Zarbo RJ, Simpson JF, Gross LK, Weiss LM (1993) Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance. Mod Pathol 6(6):721–728

    PubMed  CAS  Google Scholar 

  21. Glaser SL, Ambinder RF, DiGiuseppe JA, Horn-Ross PL, Hsu JL (1998) Absence of Epstein–Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers. Int J Cancer 75(4):555–558

    Article  PubMed  CAS  Google Scholar 

  22. Horiuchi K, Mishima K, Ohsawa M, Aozasa K (1994) Carcinoma of stomach and breast with lymphoid stroma: localization of Epstein–Barr virus. J Clin Pathol 47(6):538–540

    Article  PubMed  CAS  Google Scholar 

  23. Huang J, Chen H, Hutt-Fletcher L, Ambinder RF, Hayward SD (2003) Lytic viral replication as a contributor to the detection of Epstein–Barr virus in breast cancer. J Virol 77(24):13267–13274

    Article  PubMed  CAS  Google Scholar 

  24. Kalkan A, Ozdarendeli A, Bulut Y, Yekeler H, Cobanoglu B, Doymaz MZ (2005) Investigation of Epstein–Barr virus DNA in formalin-fixed and paraffin-embedded breast cancer tissues. Med Princ Pract 14(4):268–271

    Article  PubMed  Google Scholar 

  25. Kijima Y, Hokita S, Takao S, Baba M, Natsugoe S, Yoshinaka H, Aridome K, Otsuji T, Itoh T, Tokunaga M, Eizuru Y, Aikou T (2001) Epstein–Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms. J Med Virol 64(4):513–518

    Article  PubMed  CAS  Google Scholar 

  26. Labrecque LG, Barnes DM, Fentiman IS, Griffin BE (1995) Epstein–Barr virus in epithelial cell tumors: a breast cancer study. Cancer Res 55(1):39–45

    PubMed  CAS  Google Scholar 

  27. Luqmani YA, Shousha S (1995) Presence of Epstein–Barr virus in breast carcinoma. Int J Oncol 6:899–903

    PubMed  CAS  Google Scholar 

  28. Mazouni C, Fina F, Romain S, Ouafik L, Bonnier P, Brandone JM, Martin PM (2011) Epstein–Barr virus as a marker of biological aggressiveness in breast cancer. Br J Cancer 104(2):332–337. doi:10.1038/sj.bjc.6606048

    Article  PubMed  CAS  Google Scholar 

  29. Perkins RS, Sahm K, Marando C, Dickson-Witmer D, Pahnke GR, Mitchell M, Petrelli NJ, Berkowitz IM, Soteropoulos P, Aris VM, Dunn SP, Krueger LJ (2006) Analysis of Epstein–Barr virus reservoirs in paired blood and breast cancer primary biopsy specimens by real time PCR. Breast Cancer Res 8(6):R70. doi:10.1186/bcr1627

    Article  PubMed  Google Scholar 

  30. Perrigoue JG, den Boon JA, Friedl A, Newton MA, Ahlquist P, Sugden B (2005) Lack of association between EBV and breast carcinoma. Cancer Epidemiol Biomarkers Prev 14(4):809–814

    Article  PubMed  CAS  Google Scholar 

  31. Tsai JH, Tsai CH, Cheng MH, Lin SJ, Xu FL, Yang CC (2005) Association of viral factors with non-familial breast cancer in Taiwan by comparison with non-cancerous, fibroadenoma, and thyroid tumor tissues. J Med Virol 75(2):276–281. doi:10.1002/jmv.20267

    Article  PubMed  Google Scholar 

  32. Xue SA, Lampert IA, Haldane JS, Bridger JE, Griffin BE (2003) Epstein–Barr virus gene expression in human breast cancer: protagonist or passenger? Br J Cancer 89(1):113–119. doi:10.1038/sj.bjc.6601027

    Article  PubMed  CAS  Google Scholar 

  33. Nuovo GJ (1996) PCR in situ hybridization: Protocols and applications. Lippincott-Raven, Philadelphia

    Google Scholar 

  34. Pulvertaft JV (1964) Cytology of Burkitt’s tumor (African lymphoma). Lancet 1(7327):238–240

    Article  PubMed  CAS  Google Scholar 

  35. Pritchett R, Pedersen M, Kieff E (1976) Complexity of EBV homologous DNA in continuous lymphoblastoid cell lines. Virology 74(1):227–231

    Article  Google Scholar 

  36. Lindsey JW, Hatfield LM, Crawford MP, Patel S (2009) Quantitative PCR for Epstein–Barr virus DNA and RNA in multiple sclerosis. Mult Scler 15(2):153–158

    Article  PubMed  CAS  Google Scholar 

  37. Pinder SE, Murray S, Ellis IO, Trihia H, Elston CW, Gelber RD, Goldhirsch A, Lindtner J, Cortes-Funes H, Simoncini E, Byrne MJ, Golouh R, Rudenstam CM, Castiglione-Gertsch M, Gusterson BA (1998) The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy. Cancer 83(8):1529–1539. doi:10.1002/(SICI)1097-0142(19981015)83:8<1529:AID-CNCR7>3.0.CO;2-V

    Article  PubMed  CAS  Google Scholar 

  38. Glaser SL, Hsu JL, Gulley ML (2004) Epstein–Barr virus and breast cancer: state of the evidence for viral carcinogenesis. Cancer Epidemiol Biomarkers Prev 13(5):688–697

    PubMed  CAS  Google Scholar 

  39. Bertrand KA, Birmann BM, Chang ET, Spiegelman D, Aster JC, Zhang SM, Laden F (2010) A prospective study of Epstein–Barr virus antibodies and risk of non-Hodgkin lymphoma. Blood 116(18):3547–3553. doi:10.1182/blood-2010-05-282715

    Article  PubMed  CAS  Google Scholar 

  40. Tosato G, Steinberg AD, Yarchoan R, Heilman CA, Pike SE, De Seau V, Blaese RM (1984) Abnormally elevated frequency of Epstein–Barr virus-infected B cells in the blood of patients with rheumatoid arthritis. J Clin Invest 73(6):1789–1795. doi:10.1172/JCI111388

    Article  PubMed  CAS  Google Scholar 

  41. Shannon-Lowe C, Adland E, Bell A, Delecluse H, Rickinson A, Rowe M (2009) Features distinguishing Epstein–Barr virus infections of epithelial cells and B cells: viral genome expression, genome maintenance, and genome amplification. J Virol 83:7749–7760

    Article  PubMed  CAS  Google Scholar 

  42. Nuovo GJ (2007) The utility of in situ—based methodologies including in situ polymerase chain reaction for the diagnosis and study of viral infections. Hum Pathol 38(8):1123–1136

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We want to thank the Dr. Susan Love Research Foundation and the Avon Foundation for their support of this project. We thank Shawn Tang in the MDA pathology lab. We also thank the breast cancer patients from M. D. Anderson cancer center who donated their tissues for research.

Conflict of interest

The authors declare that they have no conflicts of interest which may have influenced the results of this study.

Author information

Authors and Affiliations

  1. Department of Family Health Care Nursing, University of California San Francisco, 2 Koret Way, N431-M, San Francisco, CA, 94143, USA

    Kimberly Baltzell

  2. Department of Global Health Science, University of California San Francisco, San Francisco, CA, USA

    Kimberly Baltzell

  3. School of Public Health, University of California, Berkeley, Berkeley, CA, USA

    Gertrude C. Buehring & Hua Min Shen

  4. Department of Pathology, M. D. Anderson Cancer Center, Houston, TX, USA

    Savitri Krishnamurthy

  5. Department of Surgical Oncology, M. D. Anderson Cancer Center, Houston, TX, USA

    Henry Kuerer

  6. Department of Neurological Surgery, University of California, San Francisco, CA, USA

    Jennette D. Sison

Authors
  1. Kimberly Baltzell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gertrude C. Buehring
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Savitri Krishnamurthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henry Kuerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hua Min Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jennette D. Sison
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kimberly Baltzell.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baltzell, K., Buehring, G.C., Krishnamurthy, S. et al. Epstein–Barr virus is seldom found in mammary epithelium of breast cancer tissue using in situ molecular methods. Breast Cancer Res Treat 132, 267–274 (2012). https://doi.org/10.1007/s10549-011-1841-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-011-1841-3

Keywords

Search

Navigation