Lack of association between Epstein–Barr virus and mammary tumours in dogs

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Introduction: Epstein–Barr virus (EBV) is a γ-herpesvirus associated with various neoplasms in humans and is a probable aetiological agent in breast cancer; however, a causal relationship has not yet been established. Because of the epidemiological and clinicopathological similarities between breast cancer and canine mammary tumours, dogs have been proposed as a valid model for breast cancer.

Material and Methods: A total of 47 canine mammary gland tumour tissues were processed by routine histopathological technique with haematoxylin-eosin staining and classified according to the type of neoplasm. DNA was extracted from paraffin-embedded tissues and the EBNA-1 gene and the BamHI-W region specific for EBV were evaluated by nested PCR.

Results: The histopathological evaluation revealed 2 benign neoplasms, and many carcinomas: 2 in situ, 9 simple, 3 solid, 10 complex, and 21 mixed. One sample was positive for the EBNA-1 gene, while all were negative for the BamHI-W region.

Conclusion: No association was found between EBV and mammary tumours in dogs. However, here we report for the first time the presence of an EBV gene sequence in a canine mammary tumour. It is likely that detection of EBV might be affected by the quality and quantity of DNA extracted from paraffin-embedded tissues. Additional studies are necessary to establish any association of EBV with mammary gland cancer in humans and in dogs, which could eventually lead to better public health prevention and control.

1. Bae J.M., Kim E.H.: Epstein-Barr Virus infection and risk of breast cancer: an adaptive meta-analysis for case-control studies. Arch Clin Infect Dis 2016, 11, e34806.

2. Blake N., Lee S., Redchenko I., Thomas W., Steven N., Leese A., Steigerwald-Mullen P., Kurilla M.G., Frappier L., Rickinson A.: Human CD8 T cell responses to EBV EBNA1: HLA class I presentation of the (Gly-Ala)-containing protein requires exogenous processing. Immunity 1997, 7, 791–802.

3. Chiou S.H., Chow K.C., Yang C.H., Chiang S.F., Lin C.H.: Discovery of Epstein-Barr Virus (EBV)-encoded RNA signal and EBV nuclear antigen leader protein DNA sequence in pet dogs. J Gen Virol 2005, 86, 899–905.

4. Chiu H.C., Chow K.C., Fan Y.H., Chang S.C., Chiou S.H., Chiang S.F., Chiou C.H., Wu G.H., Yang H.C., Ho S.P., Chen Y.K., Lee W.C., Sun H.S.: Expression of EBV-encoded oncogenes and EBV-like virions in multiple canine tumors. Vet Microbiol 2013, 163, 79–89.

5. Cinque P., Brytting M., Vago L., Castagna A., Parravicini C., Zanchetta N., Monforte A.A., Wahren B., Lazzarin A., Linde A.: Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 1993, 342, 398–401.

6. Cohen J.I.: Epstein–Barr virus infection. N Engl J Med 2000, 343, 481–492.

7. Deshpande C.G., Badve S., Kidwai N., Longnecker R.: Lack of expression of the Epstein-Barr Virus (EBV) gene products, EBERs, EBNA1, LMP1, and LMP2A, in breast cancer cells. Lab Invest 2002, 82, 1193–2002.

8. Glenn W.K., Heng B., Delprado W., Iacopetta B., Whitaker N.J., Lawson J.S.: Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer. PLoS One 2012, 7, e48788.

9. Goldschmidt M., Peña L., Rasotto R., Zappulli V.: Classification and grading of canine mammary tumors. Vet Pathol 2011, 48, 117–131.

10. Grywalska E., Rolinski J.: Epstein-Barr virus–associated lymphomas. Semin Oncol 2015, 42, 291–303.

11. Hippocrate A., Oussaief L., Joab I.: Possible role of EBV in breast cancer and other unusually EBV-associated cancers. Cancer Lett 2011, 305, 144–149.

12. Hsu J.L., Glaser S.L.: Epstein-Barr virus-associated malignancies: epidemiologic patterns and etiologic implications. Crit Rev Oncol Hematol 2000, 34, 27–53.

13. Hu H., Luo M.L., Desmedt C., Nabavi S., Yadegarynia S., Hong A., Konstantinopoulos P.A., Gabrielson E., Hines-Boykin R., Pihan G., Yuan X., Sotirious C., Dittmer D.P., Fingeroth J.D., Wulf G.M.: Epstein–Barr virus infection of mammary epithelial cells promotes malignant transformation. E Bio Medicine 2016, 9, 148–160.

14. Huang S.H., Kozak P.J., Kim J., Habineza-Ndikuyeze G., Meade C., Gaurnier-Hausser A., Patel R., Robertson E., Mason N.J.: Evidence of an oncogenic gammaherpesvirus in domestic dogs. Virology 2012, 427, 107–117.

15. Ito D., Frantz A.M., Modiano J.F.: Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications. Vet Immunol Immunopathol 2014, 159, 192–201.

16. Karayannopoulou M., Kaldrymidou E., Constantinidis T.C., Dessiris A.: Histological grading and prognosis in dogs with mammary carcinomas: application of a human grading method. J Comp Pathol 2005, 133, 246–252.

17. Klopfleisch R., Lenze D., Hummel M., Gruber A.D.: Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles. BMC Cancer 2010, 10, 618.

18. Lawson J.S., Salmons B., Glenn W.K.: Oncogenic viruses and breast cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV). Front Oncol 2018, 8, 1-18.

19. Lin J.H., Tsai C.H., Chu J.S., Chen J.Y., Takada K., Shew J.Y.: Dysregulation of HER2/HER3 signaling axis in Epstein-Barr virus-infected breast carcinoma cells. J Virol 2007, 81, 5705–5713.

20. Milman G., Smith K.C., Erles K.: Serological detection of Epstein–Barr virus infection in dogs and cats. Vet Microbiol 2011, 150, 15–20.

21. Murata T., Tsurumi T.: Switching of EBV cycles between latent and lytic states. Rev Med Virol 2014, 24, 142–153.

22. Odumade O.A., Hogquist K.A., Balfour H.H.: Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clin Microbiol Rev 2011, 24, 193–209.

23. Perrigoue J.G., Boon J.A., Friedl A., Newton M.A., Ahlquist P., Sugden B.: Lack of association between EBV and breast carcinoma. Cancer Epidemiol Biomarkers Prev 2005, 14, 809–814.

24. Raab-Traub N.: Novel mechanisms of EBV-induced oncogenesis. Curr Opin Virol 2012, 2, 453–458.

25. Rasotto R., Berlato D., Goldschmidt M.H., Zappulli V.: Prognostic significance of canine mammary tumor histologic subtypes: an observational cohort study of 229 cases. Vet Pathol 2017, 54, 571–578.

26. Rickinson A.B., Kieff E.: Epstein-Barr virus. In: Fields virology, edited by Knipe D.M., Howley P.M., Griffin D.E., Lamb R.A., Martin M.A., Roizman B., Straus S.E., Lippincott Williams & Wilkins, Philadelphia, 2001, pp. 2575–2627.

27. Sardon D., Blundell R., Burrai G.P., Alberti A., Tore G., Passino E.S., Antuofermo E.: Absence of canine papillomavirus sequences in canine mammary tumours. J Comp Pathol 2015, 152, 172–176.

28. Schulz T.F., Cordes S.: Is the Epstein–Barr virus EBNA-1 protein an oncogen? Proc Natl Acad Sci USA 2009, 106, 2091–2092.

29. Shinozaki-Ushiku A., Kunita A., Fukayama M.: Update on Epstein-Barr virus and gastric cancer. Int J Oncol 2015, 46, 1421–1434.

30. Sonmez K., Altan E., Yildirim F., Arun S.S., Turan N., Yilmaz H., Kuskucu M.A.: Investigation of human papillomaviruses (HPV), mouse mammary tumour virus (MMTV), Epstein–Barr virus (EBV), and human polyomavirus entities in canine mammary tumours. J Vet Res 2016, 60, 49–53.

31. Tomita Y., Ohsawa M., Mishiro Y., Kubo T., Maeshiro N., Kojya S., Noda Y., Aozasa K.: The presence and subtype of Epstein-Barr virus in B and T cell lymphomas of the sino-nasal region from the Osaka and Okinawa districts of Japan. Lab Invest 1995, 73, 190–196.

32. Valente A.L., Schroeder B., Shriver C.D., Henning J.D., Ellsworth R.E.: Chronic inflammation in cancer: the role of human viruses. Adv Tumor Virol 2015, 5, 1–11.

33. Waugh E.M., Gallagher A., McAulay K.A., Henriques J., Alves M., Bell A.J., Morris J.S., Jarrett R.F.: Gammaherpesviruses and canine lymphoma: no evidence for direct involvement in commonly occurring lymphomas. J Gen Virol 2015, 96, 1863–1872.

34. Young L.S., Dawson C.W.: Epstein-Barr virus and nasopharyngeal carcinoma. Chin J Cancer 2014, 33, 581–590.

35. Young L.S., Rickinson A.B.: Epstein–Barr virus: 40 years on. Nat Rev Cancer 2004, 4, 757–768.

Journal of Veterinary Research

formerly Bulletin of the Veterinary Institute in Pulawy

Journal Information

IMPACT FACTOR J Vet Res 2017: 0.811

CiteScore 2017: 0.68

SCImago Journal Rank (SJR) 2017: 0.29
Source Normalized Impact per Paper (SNIP) 2017: 0.484


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