Breast Cancer Research and Treatment

, Volume 133, Issue 3, pp 969–977 | Cite as

Investigation of human JC and BK polyomaviruses in breast carcinomas

  • Mohamed HachanaEmail author
  • Khaled Amara
  • Sonia Ziadi
  • Riadh Ben Gacem
  • Sadok Korbi
  • Mounir Trimeche
Preclinical Study


We have previously showed the presence of the simian virus 40 (SV40) and the mouse mammary tumor virus (MMTV)-like in a significant proportions of Tunisian breast carcinomas. However, to date there are no published studies concerning evaluation of the possible implication of the human polyomaviruses JC (JCV) and BK (BKV) in breast carcinomas. The presence of JCV and BKV DNA was investigated by PCR in a 123 primary breast carcinomas and matched adjacent non-tumor breast tissues. The results were correlated to clinicopathological and virological parameters. JCV T-antigen DNA was detected in 23% of breast carcinoma cases; however, all cases were negative for BKV. JCV T antigen PCR products were further confirmed as authentic JCV genome by direct sequencing. JCV was found in invasive ductal carcinomas (28/112 cases) but not in invasive lobular carcinomas (0/5) or medullary carcinomas (0/6). JCV DNA presence correlates inversely with the expression of estrogen (P = 0.022) and progesterone (P = 0.008) receptors. JCV DNA presence correlates also with “triple negative” phenotype (P = 0.021). With regard to virological data, a trend toward an inverse correlation was noted between the presence of JCV and SV40 (P = 0.06). Moreover, significant correlation was found between multiple viral infection (JCV, and/or SV40, and/or MMTV-like in the same tumor) and “triple negative” phenotype (P = 0.001) and also with p53 accumulation (P = 0.028). To the best of our knowledge, this is the first study demonstrating the presence of JCV in a subset of breast carcinomas. Also our results suggest that “triple negative” breast carcinomas are viral-related tumors.


Breast cancer Polyomaviruses BK virus JC virus Tunisia 



This study was supported by the “Ministère de l’Enseignement Supérieur, de la Recherche Scientifique et Technologie” and the “Ministère de la Santé Publique” of Tunisia.

Conflict of interest

The authors have no conflicts of interest in relation to this article.


  1. 1.
    Abdel-Aziz HO, Murai Y, Hong M, Kutsuna T, Takahashi H, Nomoto K, Murata S, Tsuneyama K, Takano Y (2007) Detection of the JC virus genome in lung cancers: possible role of the T-antigen in lung oncogenesis. Appl Immunohistochem Mol Morphol 15:394–400. doi: 10.1097/01.pai.0000213126.96590.64 PubMedCrossRefGoogle Scholar
  2. 2.
    Agostini HT, Brubaker GR, Shao J, Levin A, Ryschkewitsch CF, Blattner WA, Stoner GL (1995) BK virus and a new type of JC virus excreted by HIV-1 positive patients in rural Tanzania. Arch Virol 140:1919–1934PubMedCrossRefGoogle Scholar
  3. 3.
    Agostini HT, Ryschkewitsch CF, Stoner GL (1996) Genotype profile of human polyomavirus JC excreted in urine of immunocompetent individuals. J Clin Microbiol 34:159–164PubMedGoogle Scholar
  4. 4.
    Arthur RR, Dagostin S, Shah KV (1989) Detection of BK virus and JC virus in urine and brain tissue by the polymerase chain reaction. J Clin Microbiol 27:1174–1179PubMedGoogle Scholar
  5. 5.
    Bofill-Mas S, Girones R (2001) Excretion and transmission of JCV in human populations. J Neurovirol 7:345–349PubMedCrossRefGoogle Scholar
  6. 6.
    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 91:1376–1381PubMedCrossRefGoogle Scholar
  7. 7.
    Carbone M, Rdzanek MA, Rudzinski JJ, De Marco MA, Bocchetta M, Ramos Nino M, Mossman B, Pass HI (2005) SV40 detection in human tumor specimens. Cancer Res 65:10120–10121. doi: 10.1158/0008-5472.CAN-05-1911 PubMedCrossRefGoogle Scholar
  8. 8.
    Corallini A, Tognon M, Negrini M, Barbanti-Brodano G (2001) Evidence for BK virus as a human tumor virus. In: Khalili K, Stoner G (eds) Human polyomaviruses: molecular and clinical perspective. Wiley-Liss Inc, New York, pp 431–460Google Scholar
  9. 9.
    De Mattei M, Martini F, Corallini A, Gerosa M, Scotlandi K, Carinci P, Barbanti-Brodano G, Tognon M (1995) High incidence of BK virus large-T-antigen-coding sequences in normal human tissues and tumors of different histotypes. Int J Cancer 61:756–760PubMedCrossRefGoogle Scholar
  10. 10.
    Del Valle L, Gordon J, Assimakopoulou M, Enam S, Geddes JF, Varakis JN, Katsetos CD, Croul S, Khalili K (2001) Detection of JC virus DNA sequences and expression of the viral regulatory protein T-antigen in tumors of the central nervous system. Cancer Res 61:4287–4293PubMedGoogle Scholar
  11. 11.
    Del Valle L, Gordon J, Enam S, Delbue S, Croul S, Abraham S, Radhakrishnan S, Assimakopoulou M, Katsetos CD, Khalili K (2002) Expression of human neurotropic polyomavirus JCV late gene product agnoprotein in human medulloblastoma. J Natl Cancer Inst 94:267–273PubMedCrossRefGoogle Scholar
  12. 12.
    Del Valle L, White MK, Enam S, Oviedo SP, Bromer MQ, Thomas RM, Parkman HP, Khalili K (2005) Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma. Cancer 103:516–527. doi: 10.1002/cncr.20806 PubMedCrossRefGoogle Scholar
  13. 13.
    Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19:403–410PubMedCrossRefGoogle Scholar
  14. 14.
    Enam S, Del Valle L, Lara C, Gan DD, Ortiz-Hidalgo C, Palazzo JP, Khalili K (2002) Association of human polyomavirus JCV with colon cancer: evidence for interaction of viral T-antigen and beta-catenin. Cancer Res 62:7093–7101PubMedGoogle Scholar
  15. 15.
    Enam S, Gan DD, White MK, Del Valle L, Khalili K (2006) Regulation of human neurotropic JCV in colon cancer cells. Anticancer Res 26:833–841PubMedGoogle Scholar
  16. 16.
    Flaegstad T, Andresen PA, Johnsen JI, Asomani SK, Jorgensen GE, Vignarajan S, Kjuul A, Kogner P, Traavik T (1999) A possible contributory role of BK virus infection in neuroblastoma development. Cancer Res 59:1160–1163PubMedGoogle Scholar
  17. 17.
    Gan DD, Khalili K (2004) Interaction between JCV large T-antigen and beta-catenin. Oncogene 23:483–490. doi: 10.1038/sj.onc.1207018 PubMedCrossRefGoogle Scholar
  18. 18.
    Goel A, Li MS, Nagasaka T, Shin SK, Fuerst F, Ricciardiello L, Wasserman L, Boland CR (2006) Association of JC virus T-antigen expression with the methylator phenotype in sporadic colorectal cancers. Gastroenterology 130:1950–1961. doi: 10.1053/j.gastro.2006.02.061 PubMedCrossRefGoogle Scholar
  19. 19.
    Guo J, Kitamura T, Ebihara H, Sugimoto C, Kunitake T, Takehisa J, Na YQ, Al-Ahdal MN, Hallin A, Kawabe K, Taguchi F, Yogo Y (1996) Geographical distribution of the human polyomavirus JC virus type A and B and isolation of a new type from Ghana. J Gen Virol 77(Pt 5):919–927PubMedCrossRefGoogle Scholar
  20. 20.
    Hachana M, Trimeche M, Ziadi S, Amara K, Gaddas N, Mokni M, Korbi S (2008) Prevalence and characteristics of the MMTV-like associated breast carcinomas in Tunisia. Cancer Lett 271:222–230. doi: 10.1016/j.canlet.2008.06.001 PubMedCrossRefGoogle Scholar
  21. 21.
    Hachana M, Trimeche M, Ziadi S, Amara K, Korbi S (2009) Evidence for a role of the Simian Virus 40 in human breast carcinomas. Breast Cancer Res Treat 113:43–58. doi: 10.1007/s10549-008-9901-z PubMedCrossRefGoogle Scholar
  22. 22.
    Imperiale MJ (2000) The human polyomaviruses, BKV and JCV: molecular pathogenesis of acute disease and potential role in cancer. Virology 267:1–7. doi: 10.1006/viro.1999.0092 PubMedCrossRefGoogle Scholar
  23. 23.
    Krynska B, Del Valle L, Croul S, Gordon J, Katsetos CD, Carbone M, Giordano A, Khalili K (1999) Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogenic protein in pediatric medulloblastomas. Proc Natl Acad Sci USA 96:11519–11524PubMedCrossRefGoogle Scholar
  24. 24.
    Kunitake T, Kitamura T, Guo J, Taguchi F, Kawabe K, Yogo Y (1995) Parent-to-child transmission is relatively common in the spread of the human polyomavirus JC virus. J Clin Microbiol 33:1448–1451PubMedGoogle Scholar
  25. 25.
    Laghi L, Randolph AE, Chauhan DP, Marra G, Major EO, Neel JV, Boland CR (1999) JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci USA 96:7484–7489PubMedCrossRefGoogle Scholar
  26. 26.
    Ludlow JW (1993) Interactions between SV40 large-tumor antigen and the growth suppressor proteins pRB and p53. FASEB J 7:866–871PubMedGoogle Scholar
  27. 27.
    Major EO, Amemiya K, Tornatore CS, Houff SA, Berger JR (1992) Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 5:49–73PubMedGoogle Scholar
  28. 28.
    Murai Y, Zheng HC, Abdel Aziz HO, Mei H, Kutsuna T, Nakanishi Y, Tsuneyama K, Takano Y (2007) High JC virus load in gastric cancer and adjacent non-cancerous mucosa. Cancer Sci 98:25–31. doi: 10.1111/j.1349-7006.2006.00354.x PubMedCrossRefGoogle Scholar
  29. 29.
    Niv Y, Goel A, Boland CR (2005) JC virus and colorectal cancer: a possible trigger in the chromosomal instability pathways. Curr Opin Gastroenterol 21:85–89PubMedGoogle Scholar
  30. 30.
    Rencic A, Gordon J, Otte J, Curtis M, Kovatich A, Zoltick P, Khalili K, Andrews D (1996) Detection of JC virus DNA sequence and expression of the viral oncoprotein, tumor antigen, in brain of immunocompetent patient with oligoastrocytoma. Proc Natl Acad Sci USA 93:7352–7357PubMedCrossRefGoogle Scholar
  31. 31.
    Ricciardiello L, Baglioni M, Giovannini C, Pariali M, Cenacchi G, Ripalti A, Landini MP, Sawa H, Nagashima K, Frisque RJ, Goel A, Boland CR, Tognon M, Roda E, Bazzoli F (2003) Induction of chromosomal instability in colonic cells by the human polyomavirus JC virus. Cancer Res 63:7256–7262PubMedGoogle Scholar
  32. 32.
    Ries LAG, Eisner MP, Kosary CL (2002) SEER cancer statistics review, 1973–1999. National Cancer Institute, BethesdaGoogle Scholar
  33. 33.
    Sabin L, Wittekind C (1998) TNM classification of malignant tumours. John Wiley, New YorkGoogle Scholar
  34. 34.
    Saiki RK, Bugawan TL, Horn GT, Mullis KB, Erlich HA (1986) Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature 324:163–166. doi: 10.1038/324163a0 PubMedCrossRefGoogle Scholar
  35. 35.
    Shin SK, Li MS, Fuerst F, Hotchkiss E, Meyer R, Kim IT, Goel A, Boland CR (2006) Oncogenic T-antigen of JC virus is present frequently in human gastric cancers. Cancer 107:481–488. doi: 10.1002/cncr.22028 PubMedCrossRefGoogle Scholar
  36. 36.
    Smith RD, Galla JH, Skahan K, Anderson P, Linnemann CC Jr, Ault GS, Ryschkewitsch CF, Stoner GL (1998) Tubulointerstitial nephritis due to a mutant polyomavirus BK virus strain, BKV(Cin), causing end-stage renal disease. J Clin Microbiol 36:1660–1665PubMedGoogle Scholar
  37. 37.
    Tavassoli FA, Devilee P (eds) (2003) Pathology and genetics of tumors of the breast and female genital organs, WHO classification of tumors. IARC Press, LyonGoogle Scholar
  38. 38.
    Theodoropoulos G, Panoussopoulos D, Papaconstantinou I, Gazouli M, Perdiki M, Bramis J, Lazaris A (2005) Assessment of JC polyoma virus in colon neoplasms. Dis Colon Rectum 48:86–91PubMedCrossRefGoogle Scholar
  39. 39.
    Walsh JW, Zimmer SG, Perdue ML (1982) Role of viruses in the induction of primary intracranial tumors. Neurosurgery 10:643–662PubMedCrossRefGoogle Scholar
  40. 40.
    White MK, Gordon J, Reiss K, Del Valle L, Croul S, Giordano A, Darbinyan A, Khalili K (2005) Human polyomaviruses and brain tumors. Brain Res Brain Res Rev 50:69–85. doi: 10.1016/j.brainresrev.2005.04.007 PubMedCrossRefGoogle Scholar
  41. 41.
    Yost K, Perkins C, Cohen R, Morris C, Wright W (2001) Socioeconomic status and breast cancer incidence in California for different race/ethnic groups. Cancer Causes Control 12:703–711PubMedCrossRefGoogle Scholar
  42. 42.
    Zheng H, Abdel Aziz HO, Nakanishi Y, Masuda S, Saito H, Tsuneyama K, Takano Y (2007) Oncogenic role of JC virus in lung cancer. J Pathol 212:306–315. doi: 10.1002/path.2188 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Mohamed Hachana
    • 1
    Email author
  • Khaled Amara
    • 1
  • Sonia Ziadi
    • 1
  • Riadh Ben Gacem
    • 1
  • Sadok Korbi
    • 1
  • Mounir Trimeche
    • 1
  1. 1.Department of PathologyFarhat Hached HospitalSousseTunisia

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