Inflammatory and Non-inflammatory Breast Cancer: A Potential Role for Detection of Multiple Viral DNAs in Disease Progression
Date
2016
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Springer US
Series Info
Annals of surgical oncology;Volume: 23 Issue: 2 Pages: 494-502
Doi
Scientific Journal Rankings
Abstract
Background
Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. Multiple viral infections in IBC tissues were found to be associated with disease pathogenesis.
Objective
The aim of the present study was to correlate the incidence of viral DNA with breast cancer progression.
Materials and Methods
Overall, 135 women diagnosed with breast cancer were enrolled in this study. Using polymerase chain reaction and sequencing assays, we determined the incidence of human papillomavirus types 16 and 18 (HPV-16 and -18), human cytomegalovirus (HCMV), Epstein–Barr virus, human herpes simplex virus type 1 and 2, and human herpes virus type 8 (HHV-8) in breast carcinoma tissue biopsies. We also assessed the expression of the cell proliferation marker Ki-67 by immunohistochemistry in association with the incidence of viral DNA.
Results
HCMV and HPV-16 were the most detected viral DNAs in breast carcinoma tissues; however, the frequency of HCMV and HHV-8 DNA were significantly higher in IBC than non-IBC tissues. Moreover, the prevalence of multiple viral DNAs was higher in IBC than non-IBC tissues. The incidence of multiple viral DNAs positively correlates with tumor size and number of metastatic lymph nodes in both non-IBC and IBC patients. The expression of Ki-67 was found to be significantly higher in both non-IBC and IBC tissues in which multiple viral DNAs were detected.
Conclusions
The incidence of multiple viral DNAs in IBC tissues was higher compared with non-IBC tissues. The present results suggest the possibility of a functional relationship between the presence of multiple viral DNAs and disease pathogenesis.
Description
MSA Google Scholar
Keywords
University of Metastatic Lymph Node; Lymphovascular Invasion; Inflammatory Breast Cancer; HCMV Infection; Inflammatory Breast Cancer Patient
Citation
1. Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol. 2001;2(3):133–140. PubMed CAS Article Google Scholar 2. van Diest PJ, van der Wall E, Baak JP. Prognostic value of proliferation in invasive breast cancer: a review. J Clin Pathol. 2004;57(7):675–681. PubMed PubMed Central Article Google Scholar 3. Ellis LM, Fidler IJ. Angiogenesis and metastasis. Eur J Cancer. 1996;32A(14):2451–2460. PubMed CAS Article Google Scholar 4. Dowsett M, Nielsen TO, A’Hern R, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer Working Group. J Natl Cancer Inst. 2011;103(22):1656–1664. PubMed CAS PubMed Central Article Google Scholar 5. Schonk DM, Kuijpers HJ, van Drunen E, et al. Assignment of the gene(s) involved in the expression of the proliferation-related Ki-67 antigen to human chromosome 10. Hum Genet. 1989;83(3):297–299. PubMed CAS Article Google Scholar 6. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182(3):311–322. PubMed CAS Article Google Scholar 7. Thor AD, Liu S, Moore DH 2nd, Edgerton SM. Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol. 1999;17(2):470–477. PubMed CAS Google Scholar 8. Haroon S, Hashmi AA, Khurshid A, et al. Ki67 index in breast cancer: correlation with other prognostic markers and potential in Pakistani patients. Asian Pac J Cancer Prev. 2013;14(7):4353–4358. PubMed Article Google Scholar 9. Colozza M, Azambuja E, Cardoso F, Sotiriou C, Larsimont D, Piccart MJ. Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann Oncol. 2005;16(11):1723–1739. PubMed CAS Article Google Scholar 10. Yahia ZA, Adam AA, Elgizouli M, et al. Epstein Barr virus: a prime candidate of breast cancer aetiology in Sudanese patients. Infect Agent Cancer. 2014;9(1):9. PubMed PubMed Central Article Google Scholar 11. Taher C, de Boniface J, Mohammad AA, et al. High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes. PloS One. 2013;8(2):e56795. PubMed CAS PubMed Central Article Google Scholar 12. Tsai JH, Tsai CH, Cheng MH, Lin SJ, Xu FL, Yang CC. Association of viral factors with non-familial breast cancer in Taiwan by comparison with non-cancerous, fibroadenoma, and thyroid tumor tissues. J Med Virol. 2005;75(2):276–281. PubMed Article Google Scholar 13. Wang T, Chang P, Wang L, et al. The role of human papillomavirus infection in breast cancer. Med Oncol. 2012;29(1):48–55. PubMed Article Google Scholar 14. Wang-Johanning F, Frost AR, Johanning GL, et al. Expression of human endogenous retrovirus k envelope transcripts in human breast cancer. Clin Cancer Res. 2001;7(6):1553–1560. PubMed CAS Google Scholar 15. Antonsson A, Bialasiewicz S, Rockett RJ, Jacob K, Bennett IC, Sloots TP. Exploring the prevalence of ten polyomaviruses and two herpes viruses in breast cancer. PloS One. 2012;7(8):e39842. PubMed CAS PubMed Central Article Google Scholar 16. Cai Q, Chen K, Young KH. Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders. Exp Mol Med. 2015;47:e133. PubMed CAS PubMed Central Article Google Scholar 17. Arbach H, Viglasky V, Lefeu F, et al. 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. 2006;80(2):845–853. PubMed CAS PubMed Central Article Google Scholar 18. Samols MA, Skalsky RL, Maldonado AM, et al. Identification of cellular genes targeted by KSHV-encoded microRNAs. PLoS Pathog. 2007;3(5):e65. PubMed PubMed Central Article Google Scholar 19. Taraboletti G, Benelli R, Borsotti P, et al. Thrombospondin-1 inhibits Kaposi’s sarcoma (KS) cell and HIV-1 Tat-induced angiogenesis and is poorly expressed in KS lesions. J Pathol. 1999;188(1):76–81. PubMed CAS Article Google Scholar 20. Alibek K, Kakpenova A, Mussabekova A, Sypabekova M, Karatayeva N. Role of viruses in the development of breast cancer. Infect Agent Cancer. 2013;8:32. PubMed PubMed Central Article Google Scholar 21. El-Shinawi M, Mohamed HT, El-Ghonaimy EA, et al. Human cytomegalovirus infection enhances NF-kappaB/p65 signaling in inflammatory breast cancer patients. PloS One. 2013;8(2):e55755. PubMed CAS PubMed Central Article Google Scholar 22. Maussang D, Verzijl D, van Walsum M, et al. Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis. Proc Natl Acad Sci USA. 2006;103(35):13068–13073. PubMed CAS PubMed Central Article Google Scholar 23. Skaletskaya A, Bartle LM, Chittenden T, McCormick AL, Mocarski ES, Goldmacher VS. A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Proc Natl Acad Sci USA. 2001;98(14):7829–7834. PubMed CAS PubMed Central Article Google Scholar 24. Munger J, Roizman B. The US3 protein kinase of herpes simplex virus 1 mediates the posttranslational modification of BAD and prevents BAD-induced programmed cell death in the absence of other viral proteins. Proc Natl Acad Sci USA. 2001;98(18):10410–10415. PubMed CAS PubMed Central Article Google Scholar 25. Ogg PD, McDonell PJ, Ryckman BJ, Knudson CM, Roller RJ. The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members. Virology. 2004;319(2):212–224. PubMed CAS Article Google Scholar 26. Simoes PW, Medeiros LR, Simoes Pires PD, et al. Prevalence of human papillomavirus in breast cancer: a systematic review. Int J Gynecol Cancer. 2012;22(3):343–347. PubMed Article Google Scholar 27. Sengupta S, Biarnes MC, Jordan VC. Cyclin dependent kinase-9 mediated transcriptional de-regulation of cMYC as a critical determinant of endocrine-therapy resistance in breast cancers. Breast Cancer Res Treat. 2014;143(1):113–124. PubMed CAS PubMed Central Article Google Scholar 28. Ferber MJ, Thorland EC, Brink AA, et al. Preferential integration of human papillomavirus type 18 near the c-Myc locus in cervical carcinoma. Oncogene. 2003;22(46):7233–7242. PubMed CAS Article Google Scholar 29. McMurray HR, McCance DJ. Human papillomavirus type 16 E6 activates TERT gene transcription through induction of c-Myc and release of USF-mediated repression. J Virol. 2003;77(18):9852–9861. PubMed CAS PubMed Central Article Google Scholar 30. Nouh MA, Mohamed MM, El-Shinawi M, et al. Cathepsin B: a potential prognostic marker for inflammatory breast cancer. J Transl Med. 2011;9:1. PubMed CAS PubMed Central Article Google Scholar 31. Chang S, Parker SL, Pham T, Buzdar AU, Hursting SD. Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992. Cancer. 1998;82(12):2366–2372. PubMed CAS Article Google Scholar 32. Damin AP, Karam R, Zettler CG, Caleffi M, Alexandre CO. Evidence for an association of human papillomavirus and breast carcinomas. Breast Cancer Res Treat. 2004;84(2):131–137. PubMed CAS Article Google Scholar 33. Hennig EM, Suo Z, Thoresen S, Holm R, Kvinnsland S, Nesland JM. Human papillomavirus 16 in breast cancer of women treated for high grade cervical intraepithelial neoplasia (CIN III). Breast Cancer Res Treat. 1999;53(2):121–135. PubMed CAS Article Google Scholar 34. Guo M, Sneige N, Silva EG, et al. Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma. Mod Pathol. 2007;20(2):256–266. PubMed CAS Article Google Scholar 35. Mohamed MM, Sabet S, Peng DF, Nouh MA, El-Shinawi M, El-Rifai W. Promoter hypermethylation and suppression of glutathione peroxidase 3 are associated with inflammatory breast carcinogenesis. Oxid Med Cell Longev. 2014;2014:787195. PubMed PubMed Central Google Scholar 36. El-Ghonaimy EA, El-Shinawi M, Ibrahim SA, et al. Positive lymph-node breast cancer patients: activation of NF-kappaB in tumor-associated leukocytes stimulates cytokine secretion that promotes metastasis via C-C chemokine receptor CCR7. FEBS J. 2015;282(2):271–282. PubMed CAS Article Google Scholar 37. Mohamed MM, El-Ghonaimy EA, Nouh MA, Schneider RJ, Sloane BF, El-Shinawi M. Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties. Int J Biochem Cell Biol. 2014;46:138–147. PubMed CAS PubMed Central Article Google Scholar 38. Mohamed HT, El-Shinawi M, Nouh MA, et al. Inflammatory breast cancer: high incidence of detection of mixed human cytomegalovirus genotypes associated with disease pathogenesis. Front Oncol. 2014;4:246. PubMed PubMed Central Article Google Scholar 39. Harkins LE, Matlaf LA, Soroceanu L, et al. Detection of human cytomegalovirus in normal and neoplastic breast epithelium. Herpesviridae. 2010;1(1):8. PubMed PubMed Central Article Google Scholar 40. Huo Q, Zhang N, Yang Q. Epstein-Barr virus infection and sporadic breast cancer risk: a meta-analysis. PloS One. 2012;7(2):e31656. PubMed CAS PubMed Central Article Google Scholar 41. Kan CY, Iacopetta BJ, Lawson JS, Whitaker NJ. Identification of human papillomavirus DNA gene sequences in human breast cancer. Br J Cancer. 2005;93(8):946–948. PubMed CAS PubMed Central Article Google Scholar 42. Lawson JS, Glenn WK, Heng B, et al. Koilocytes indicate a role for human papilloma virus in breast cancer. Br J Cancer. 2009;101(8):1351–1356. PubMed CAS PubMed Central Article Google Scholar 43. Tsai JH, Hsu CS, Tsai CH, et al. Relationship between viral factors, axillary lymph node status and survival in breast cancer. J Cancer Res Clin Oncol. 2007;133(1):13–21. PubMed Article Google Scholar 44. Gumus M, Yumuk PF, Salepci T, et al. HPV DNA frequency and subset analysis in human breast cancer patients’ normal and tumoral tissue samples. J Exp Clin Cancer Res. 2006;25(4):515–521. PubMed CAS Google Scholar 45. Corbex M, Bouzbid S, Traverse-Glehen A, et al. Prevalence of papillomaviruses, polyomaviruses, and herpesviruses in triple-negative and inflammatory breast tumors from algeria compared with other types of breast cancer tumors. PloS One. 2014;9(12):e114559. PubMed PubMed Central Article Google Scholar 46. Fimereli D, Gacquer D, Fumagalli D, et al. No significant viral transcription detected in whole breast cancer transcriptomes. BMC Cancer. 2015;15:147. PubMed PubMed Central Article Google Scholar 47. Tang KW, Alaei-Mahabadi B, Samuelsson T, Lindh M, Larsson E. The landscape of viral expression and host gene fusion and adaptation in human cancer. Nat Commun. 2013;4:2513. PubMed PubMed Central Google Scholar 48. Khabaz MN. Association of Epstein-Barr virus infection and breast carcinoma. Arch Med Sci. 2013;9(4):745–751. PubMed CAS PubMed Central Article Google Scholar 49. Glenn WK, Heng B, Delprado W, Iacopetta B, Whitaker NJ, Lawson JS. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer. PloS One. 2012;7(11):e48788. PubMed CAS PubMed Central Article Google Scholar 50. Chen T-M, Chang C-F, Chen Y-H, Chen C-A, Wu C-C, Hsieh C-Y. Coexistence of human cytomegalovirus and human papillomavirus type 16 correlates with lymph node metastasis in cervical cancer. J Cancer Res Clin Oncol. 1996;122(10):3. Article Google Scholar 51. Mohamed MM, Al-Raawi D, Sabet SF, El-Shinawi M. Inflammatory breast cancer: New factors contribute to disease etiology: a review. J Adv Res. 2014;5(5):525–536. PubMed CAS PubMed Central Article Google Scholar 52. Al-Raawi D, Abu-El-Zahab H, El-Shinawi M, Mohamed MM. Membrane type-1 matrix metalloproteinase (MT1-MMP) correlates with the expression and activation of matrix metalloproteinase-2 (MMP-2) in inflammatory breast cancer. Int J Clin Exp Med. 2011;4(4):265–275. PubMed CAS PubMed Central Google Scholar 53. de Oliveira DE, Bacchi MM, Macarenco RS, Tagliarini JV, Cordeiro RC, Bacchi CE. Human papillomavirus and Epstein-Barr virus infection, p53 expression, and cellular proliferation in laryngeal carcinoma. Am J Clin Pathol. 2006;126(2):284–293. PubMed Article Google Scholar 54. Qi ZL, Huo X, Xu XJ, et al. Relationship between HPV16/18 E6 and 53, 21WAF1, MDM2, Ki67 and cyclin D1 expression in esophageal squamous cell carcinoma: comparative study by using tissue microarray technology. Exp Oncol. 2006;28(3):235–240. PubMed CAS Google Scholar 55. Mate JL, Ariza A, Munoz A, Molinero JL, Lopez D, Navas-Palacios JJ. Induction of proliferating cell nuclear antigen and Ki-67 expression by cytomegalovirus infection. J Pathol. 1998;184(3):279–282. PubMed CAS Article Google Scholar 56. Zheng X, Hu L, Chen F, Christensson B. Expression of Ki67 antigen, epidermal growth factor receptor and Epstein-Barr virus-encoded latent membrane protein (LMP1) in nasopharyngeal carcinoma. Eur J Cancer B. 1994;30B(5):290–295.