Inflammatory breast cancer: high incidence of detection of mixed human cytomegalovirus genotypes associated with disease pathogenesis
Date
2014
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Frontiers
Series Info
Frontiers in oncology;Volume: 4
Doi
Scientific Journal Rankings
Abstract
Inflammatory breast cancer (IBC) is a highly metastatic, aggressive, and fatal form of breast cancer. Patients presenting with IBC are characterized by a high number of axillary lymph node metastases. Recently, we found that IBC carcinoma tissues contain significantly higher levels of human cytomegalovirus (HCMV) DNA compared to other breast cancer tissues that may regulate cell signaling pathways. In fact, HCMV pathogenesis and clinical outcome can be statistically associated with multiple HCMV genotypes within IBC. Thus, in the present study, we established the incidence and types of HCMV genotypes present in carcinoma tissues of infected non-IBC versus IBC patients. We also assessed the correlation between detection of mixed genotypes of HCMV and disease progression. Genotyping of HCMV in carcinoma tissues revealed that glycoprotein B (gB)-1 and glycoprotein N (gN)-1 were the most prevalent HCMV genotypes in both non-IBC and IBC patients with no significant difference between patients groups. IBC carcinoma tissues, however, showed statistically significant higher incidence of detection of the gN-3b genotype compared to non-IBC patients. The incidence of detection of mixed genotypes of gB showed that gB-1 + gB-3 was statistically significantly higher in IBC than non-IBC patients. Similarly, the incidence of detection of mixed genotypes of gN showed that gN-1 + gN-3b and gN-3 + gN-4b/c were statistically significant higher in the carcinoma tissues of IBC than non-IBC. Mixed presence of different HCMV genotypes was found to be significantly correlated with the number of metastatic lymph nodes in non-IBC but not in IBC patients. In IBC, detection of mixed HCMV different genotypes significantly correlates with lymphovascular invasion and formation of dermal lymphatic emboli, which was not found in non-IBC patients.
Description
MSA Google Scholar
Keywords
University of human cytomegalovirus, glycoproteins, inflammatory breast neoplasms, UL55, UL73, lymphovascular invasion, metastasis
Citation
1. Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol (2001) 2(3):133–40. doi:10.1016/S1470-2045(00)00254-0 CrossRef Full Text 2. Anders CK, Carey LA. Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer. Clin Breast Cancer (2009) 9(Suppl 2):S73–81. doi:10.3816/CBC.2009.s.008 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 3. Hsu CR, Lu TM, Chin LW, Yang CC. Possible DNA viral factors of human breast cancer. Cancers (Basel) (2010) 2(2):498–512. doi:10.3390/cancers2020498 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 4. Lawson JS, Heng B. Viruses and breast cancer. Cancers (Basel) (2010) 2(2):752–72. doi:10.3390/cancers2020752 CrossRef Full Text 5. Joshi D, Quadri M, Gangane N, Joshi R. Association of Epstein Barr virus infection (EBV) with breast cancer in rural Indian women. PLoS One (2009) 4(12):e8180. doi:10.1371/journal.pone.0008180 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 6. Tsai JH, Hsu CS, Tsai CH, Su JM, Liu YT, Cheng MH, 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. doi:10.1007/s00432-006-0141-5 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 7. Melana SM, Nepomnaschy I, Hasa J, Djougarian A, Holland JF, Pogo BG. Detection of human mammary tumor virus proteins in human breast cancer cells. J Virol Methods (2010) 163(1):157–61. doi:10.1016/j.jviromet.2009.09.015 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 8. Harkins LE, Matlaf LA, Soroceanu L, Klemm K, Britt WJ, Wang W, et al. Detection of human cytomegalovirus in normal and neoplastic breast epithelium. Herpesviridae (2010) 1(1):8. doi:10.1186/2042-4280-1-8 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 9. Fagundes CP, Glaser R, Alfano CM, Bennett JM, Povoski SP, Lipari AM, et al. Fatigue and herpesvirus latency in women newly diagnosed with breast cancer. Brain Behav Immun (2012) 26(3):394–400. doi:10.1016/j.bbi.2011.09.014 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 10. Breathnach O, Donnellan P, Collins D, McNicholas W, Crown J. Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: case report and review of the literature. Ann Oncol (1999) 10(4):461–5. doi:10.1023/A:1008360927507 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 11. Redpath S, Angulo A, Gascoigne NR, Ghazal P. Murine cytomegalovirus infection down-regulates MHC class II expression on macrophages by induction of IL-10. J Immunol (1999) 162(11):6701–7. Pubmed Abstract | Pubmed Full Text 12. Dumortier J, Streblow DN, Moses AV, Jacobs JM, Kreklywich CN, Camp D, et al. Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing. J Virol (2008) 82(13):6524–35. doi:10.1128/JVI.00502-08 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 13. Juckem LK, Boehme KW, Feire AL, Compton T. Differential initiation of innate immune responses induced by human cytomegalovirus entry into fibroblast cells. J Immunol (2008) 180(7):4965–77. doi:10.4049/jimmunol.180.7.4965 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 14. Meyer-Konig U, Ebert K, Schrage B, Pollak S, Hufert FT. Simultaneous infection of healthy people with multiple human cytomegalovirus strains. Lancet (1998) 352(9136):1280–1. doi:10.1016/S0140-6736(05)70487-6 CrossRef Full Text 15. Coaquette A, Bourgeois A, Dirand C, Varin A, Chen W, Herbein G. Mixed cytomegalovirus glycoprotein B genotypes in immunocompromised patients. Clin Infect Dis (2004) 39(2):155–61. doi:10.1086/421496 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 16. Halary F, Amara A, Lortat-Jacob H, Messerle M, Delaunay T, Houles C, et al. Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. Immunity (2002) 17(5):653–64. doi:10.1016/S1074-7613(02)00447-8 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 17. Dolan A, Cunningham C, Hector RD, Hassan-Walker AF, Lee L, Addison C, et al. Genetic content of wild-type human cytomegalovirus. J Gen Virol (2004) 85(Pt 5):1301–12. doi:10.1099/vir.0.79888-0 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 18. Pignatelli S, Dal Monte P, Rossini G, Landini MP. Genetic polymorphisms among human cytomegalovirus (HCMV) wild-type strains. Rev Med Virol (2004) 14(6):383–410. doi:10.1002/rmv.438 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 19. Pignatelli S, Dal Monte P, Rossini G, Chou S, Gojobori T, Hanada K, et al. Human cytomegalovirus glycoprotein N (gpUL73-gN) genomic variants: identification of a novel subgroup, geographical distribution and evidence of positive selective pressure. J Gen Virol (2003) 84(Pt 3):647–55. doi:10.1099/vir.0.18704-0 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 20. Shepp DH, Match ME, Lipson SM, Pergolizzi RG. A fifth human cytomegalovirus glycoprotein B genotype. Res Virol (1998) 149(2):109–14. doi:10.1016/S0923-2516(98)80086-1 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 21. Pignatelli S, Dal Monte P, Rossini G, Camozzi D, Toscano V, Conte R, et al. Latency-associated human cytomegalovirus glycoprotein N genotypes in monocytes from healthy blood donors. Transfusion (2006) 46(10):1754–62. doi:10.1111/j.1537-2995.2006.00963.x Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 22. Feire AL, Roy RM, Manley K, Compton T. The glycoprotein B disintegrin-like domain binds beta 1 integrin to mediate cytomegalovirus entry. J Virol (2010) 84(19):10026–37. doi:10.1128/JVI.00710-10 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 23. Feire AL, Koss H, Compton T. Cellular integrins function as entry receptors for human cytomegalovirus via a highly conserved disintegrin-like domain. Proc Natl Acad Sci U S A (2004) 101(43):15470–5. doi:10.1073/pnas.0406821101 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 24. Wen Y, Monroe J, Linton C, Archer J, Beard CW, Barnett SW, et al. Human cytomegalovirus gH/gL/UL128/UL130/UL131A complex elicits potently neutralizing antibodies in mice. Vaccine (2014) 32(30):3796–804. doi:10.1016/j.vaccine.2014.05.004 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 25. Simmen KA, Singh J, Luukkonen BG, Lopper M, Bittner A, Miller NE, et al. Global modulation of cellular transcription by human cytomegalovirus is initiated by viral glycoprotein B. Proc Natl Acad Sci U S A (2001) 98(13):7140–5. doi:10.1073/pnas.121177598 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 26. Kropff B, Burkhardt C, Schott J, Nentwich J, Fisch T, Britt W, et al. Glycoprotein N of human cytomegalovirus protects the virus from neutralizing antibodies. PLoS Pathog (2012) 8(10):e1002999. doi:10.1371/journal.ppat.1002999 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 27. Johnson RA, Huong SM, Huang ES. Activation of the mitogen-activated protein kinase p38 by human cytomegalovirus infection through two distinct pathways: a novel mechanism for activation of p38. J Virol (2000) 74(3):1158–67. doi:10.1128/JVI.74.3.1158-1167.2000 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 28. Johnson RA, Wang X, Ma XL, Huong SM, Huang ES. Human cytomegalovirus up-regulates the phosphatidylinositol 3-kinase (PI3-K) pathway: inhibition of PI3-K activity inhibits viral replication and virus-induced signaling. J Virol (2001) 75(13):6022–32. doi:10.1128/JVI.75.13.6022-6032.2001 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 29. Luo M, Guan JL. Focal adhesion kinase: a prominent determinant in breast cancer initiation, progression and metastasis. Cancer Lett (2010) 289(2):127–39. doi:10.1016/j.canlet.2009.07.005 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 30. Adeyinka A, Nui Y, Cherlet T, Snell L, Watson PH, Murphy LC. Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression. Clin Cancer Res (2002) 8(6):1747–53. Pubmed Abstract | Pubmed Full Text 31. Brader S, Eccles SA. Phosphoinositide 3-kinase signalling pathways in tumor progression, invasion and angiogenesis. Tumori (2004) 90(1):2–8. Pubmed Abstract | Pubmed Full Text 32. Cinatl J, Scholz M, Kotchetkov R, Vogel JU, Doerr HW. Molecular mechanisms of the modulatory effects of HCMV infection in tumor cell biology. Trends Mol Med (2004) 10(1):19–23. doi:10.1016/j.molmed.2003.11.002 CrossRef Full Text 33. Gorzer I, Kerschner H, Redlberger-Fritz M, Puchhammer-Stockl E. Human cytomegalovirus (HCMV) genotype populations in immunocompetent individuals during primary HCMV infection. J Clin Virol (2010) 48(2):100–3. doi:10.1016/j.jcv.2010.03.005 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 34. Bates M, Monze M, Bima H, Kapambwe M, Kasolo FC, Gompels UA. High human cytomegalovirus loads and diverse linked variable genotypes in both HIV-1 infected and exposed, but uninfected, children in Africa. Virology (2008) 382(1):28–36. doi:10.1016/j.virol.2008.09.001 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 35. Pang X, Humar A, Preiksaitis JK. Concurrent genotyping and quantitation of cytomegalovirus gB genotypes in solid-organ-transplant recipients by use of a real-time PCR assay. J Clin Microbiol (2008) 46(12):4004–10. doi:10.1128/JCM.01341-08 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 36. Lisboa LF, Kumar D, Wilson LE, Humar A. Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia. Transplantation (2012) 93(2):195–200. doi:10.1097/TP.0b013e31823c1cd4 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 37. Mohamed MM. Monocytes conditioned media stimulate fibronectin expression and spreading of inflammatory breast cancer cells in three-dimensional culture: a mechanism mediated by IL-8 signaling pathway. Cell Commun Signal (2012) 10(1):3. doi:10.1186/1478-811X-10-3 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 38. Mohamed MM, Cavallo-Medved D, Sloane BF. Human monocytes augment invasiveness and proteolytic activity of inflammatory breast cancer. Biol Chem (2008) 389(8):1117–21. doi:10.1515/BC.2008.117 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 39. 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. doi:10.1155/2014/787195 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 40. Nouh MA, Mohamed MM, El-Shinawi M, Shaalan MA, Cavallo-Medved D, Khaled HM, et al. Cathepsin B: a potential prognostic marker for inflammatory breast cancer. J Transl Med (2011) 9:1. doi:10.1186/1479-5876-9-1 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 41. Victor BC, Anbalagan A, Mohamed MM, Sloane BF, Cavallo-Medved D. Inhibition of cathepsin B activity attenuates extracellular matrix degradation and inflammatory breast cancer invasion. Breast Cancer Res (2011) 13(6):R115. doi:10.1186/bcr3058 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 42. 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) 46:138–47. doi:10.1016/j.biocel.2013.11.015 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 43. El-Shinawi M, Mohamed HT, El-Ghonaimy EA, Tantawy M, Younis A, Schneider RJ, et al. Human cytomegalovirus infection enhances NF-kappaB/p65 signaling in inflammatory breast cancer patients. PLoS One (2013) 8(2):e55755. doi:10.1371/journal.pone.0055755 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 44. Tarrago D, Quereda C, Tenorio A. Different cytomegalovirus glycoprotein B genotype distribution in serum and cerebrospinal fluid specimens determined by a novel multiplex nested PCR. J Clin Microbiol (2003) 41(7):2872–7. doi:10.1128/JCM.41.7.2872-2877.2003 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 45. Pignatelli S, Maurizio D, Ladini MP, Dal Monte P. Development of a multiplex PCR for the simultaneous amplification and genotyping of glycoprotein N among human cytomegalovirus strains. New Microbiol (2010) 33(3):257–62. Pubmed Abstract | Pubmed Full Text 46. Yan H, Koyano S, Inami Y, Yamamoto Y, Suzutani T, Mizuguchi M, et al. Genetic linkage among human cytomegalovirus glycoprotein N (gN) and gO genes, with evidence for recombination from congenitally and post-natally infected Japanese infants. J Gen Virol (2008) 89(Pt 9):2275–9. doi:10.1099/vir.0.83685-0 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 47. Brower V. Accidental passengers or perpetrators? Current virus-cancer research. J Natl Cancer Inst (2004) 96(4):257–8. doi:10.1093/jnci/96.4.257 CrossRef Full Text 48. Chou S. Comparative analysis of sequence variation in gp116 and gp55 components of glycoprotein B of human cytomegalovirus. Virology (1992) 188(1):388–90. doi:10.1016/0042-6822(92)90771-G Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 49. Fries BC, Chou S, Boeckh M, Torok-Storb B. Frequency distribution of cytomegalovirus envelope glycoprotein genotypes in bone marrow transplant recipients. J Infect Dis (1994) 169(4):769–74. doi:10.1093/infdis/169.4.769 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 50. Cicin-Sain L, Podlech J, Messerle M, Reddehase MJ, Koszinowski UH. Frequent coinfection of cells explains functional in vivo complementation between cytomegalovirus variants in the multiply infected host. J Virol (2005) 79(15):9492–502. doi:10.1128/JVI.79.15.9492-9502.2005 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 51. Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest (2011) 121(10):3804–9. doi:10.1172/JCI57099 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 52. Mohamed MM, Cavallo-Medved D, Rudy D, Anbalagan A, Moin K, Sloane BF. Interleukin-6 increases expression and secretion of cathepsin B by breast tumor-associated monocytes. Cell Physiol Biochem (2010) 25(2–3):315–24. doi:10.1159/000276564 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 53. Chandler SH, McDougall JK. Comparison of restriction site polymorphisms among clinical isolates and laboratory strains of human cytomegalovirus. J Gen Virol (1986) 67(Pt 10):2179–92. doi:10.1099/0022-1317-67-10-2179 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 54. Navarro D, Paz P, Tugizov S, Topp K, La Vail J, Pereira L. Glycoprotein B of human cytomegalovirus promotes virion penetration into cells, transmission of infection from cell to cell, and fusion of infected cells. Virology (1993) 197(1):143–58. doi:10.1006/viro.1993.1575 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 55. Cranage MP, Kouzarides T, Bankier AT, Satchwell S, Weston K, Tomlinson P, et al. Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus. EMBO J (1986) 5(11):3057–63. Pubmed Abstract | Pubmed Full Text 56. Kari B, Gehrz R. Structure, composition and heparin binding properties of a human cytomegalovirus glycoprotein complex designated gC-II. J Gen Virol (1993) 74(Pt 2):255–64. doi:10.1099/0022-1317-74-2-255 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 57. Madi N, Al-Nakib W, Pacsa A, Saeed T. Cytomegalovirus genotypes gB1 and gH1 are the most predominant genotypes among renal transplant recipients in Kuwait. Transplant Proc (2011) 43(5):1634–7. doi:10.1016/j.transproceed.2011.02.053 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 58. Paca-Uccaralertkun S, Hiatt R, Leecharoen R, Tan-Ariya P, Mungthin M, Pongphong S. Human cytomegalovirus gB1 genotypes among children who live at the Phayathai Babies’ home in Nonthaburi, Thailand. Southeast Asian J Trop Med Public Health (2013) 44(4):636–40. Pubmed Abstract | Pubmed Full Text 59. Jin H, Wang X, Li S. Human cytomegalovirus glycoprotein B genotype correlates with different symptoms of infected infants. Intervirology (2007) 50(3):219–23. doi:10.1159/000100564 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 60. Zhang MG, Wang HB, Wang YZ, Pan Q. [Human cytomegalovirus glycoprotein B genotypes in congenitally infected neonates]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi (2011) 25(4):262–4. Pubmed Abstract | Pubmed Full Text 61. Lukacsi A, Tarodi B, Endreffy E, Babinszki A, Pal A, Pusztai R. Human cytomegalovirus gB genotype 1 is dominant in congenital infections in South Hungary. J Med Virol (2001) 65(3):537–42. doi:10.1002/jmv.2070 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 62. Yamamoto AY, Mussi-Pinhata MM, de Deus Wagatsuma VM, Marin LJ, Duarte G, Figueiredo LT. Human cytomegalovirus glycoprotein B genotypes in Brazilian mothers and their congenitally infected infants. J Med Virol (2007) 79(8):1164–8. doi:10.1002/jmv.20903 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 63. Novak Z, Ross SA, Patro RK, Pati SK, Kumbla RA, Brice S, et al. Cytomegalovirus strain diversity in seropositive women. J Clin Microbiol (2008) 46(3):882–6. doi:10.1128/JCM.01079-07 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 64. Ross SA, Novak Z, Ashrith G, Rivera LB, Britt WJ, Hedges S, et al. Association between genital tract cytomegalovirus infection and bacterial vaginosis. J Infect Dis (2005) 192(10):1727–30. doi:10.1086/497150 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 65. Sowmya P, Madhavan HN. Analysis of mixed infections by multiple genotypes of human cytomegalovirus in immunocompromised patients. J Med Virol (2009) 81(5):861–9. doi:10.1002/jmv.21459 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 66. Lehman HL, Van Laere SJ, van Golen CM, Vermeulen PB, Dirix LY, van Golen KL. Regulation of inflammatory breast cancer cell invasion through Akt1/PKBalpha phosphorylation of RhoC GTPase. Mol Cancer Res (2012) 10(10):1306–18. doi:10.1158/1541-7786.MCR-12-0173 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 67. Nogueira E, Ozaki KS, Tomiyama H, Camara NO, Granato CF. Clinical correlations of human cytomegalovirus strains and viral load in kidney transplant recipients. Int Immunopharmacol (2009) 9(1):26–31. doi:10.1016/j.intimp.2008.08.020 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 68. Wu X, Wang Y, Xu Y, Wu D, Sun A, Zhu Z, et al. Cytomegalovirus glycoprotein B genotype in hematopoietic stem cell transplant patients from China. Biol Blood Marrow Transplant (2010) 16(5):647–52. doi:10.1016/j.bbmt.2009.12.001 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 69. Dieamant DC, Bonon SH, Peres RM, Costa CR, Albuquerque DM, Miranda EC, et al. Cytomegalovirus (CMV) genotype in allogeneic hematopoietic stem cell transplantation. BMC Infect Dis (2013) 13:310. doi:10.1186/1471-2334-13-310 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 70. Torok-Storb B, Boeckh M, Hoy C, Leisenring W, Myerson D, Gooley T. Association of specific cytomegalovirus genotypes with death from myelosuppression after marrow transplantation. Blood (1997) 90(5):2097–102. Pubmed Abstract | Pubmed Full Text 71. Picone O, Costa JM, Chaix ML, Ville Y, Rouzioux C, Leruez-Ville M. Human cytomegalovirus UL144 gene polymorphisms in congenital infections. J Clin Microbiol (2005) 43(1):25–9. doi:10.1128/JCM.43.1.25-29.2005 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 72. Pignatelli S, Lazzarotto T, Gatto MR, Dal Monte P, Landini MP, Faldella G, et al. Cytomegalovirus gN genotypes distribution among congenitally infected newborns and their relationship with symptoms at birth and sequelae. Clin Infect Dis (2010) 51(1):33–41. doi:10.1086/653423 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 73. Kett K, Szilagyi K, Anga B, Kett AG, Kiralyfalvi K. Axillary lymph drainage as a prognostic factor of survival in breast cancer. Lymphology (2002) 35(4):161–70. Pubmed Abstract | Pubmed Full Text 74. Taher C, de Boniface J, Mohammad AA, Religa P, Hartman J, Yaiw KC, 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. doi:10.1371/journal.pone.0056795 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 75. Tzer-Ming C, Chin-Feng C, Yen-Hui C, Chi-An C, Chih-Chen W, Chang-Yao H. 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. 76. Fiorentini S, Luganini A, Dell’Oste V, Lorusso B, Cervi E, Caccuri F, et al. Human cytomegalovirus productively infects lymphatic endothelial cells and induces a secretome that promotes angiogenesis and lymphangiogenesis through interleukin-6 and granulocyte-macrophage colony-stimulating factor. J Gen Virol (2011) 92(Pt 3):650–60. doi:10.1099/vir.0.025395-0 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 77. Soroceanu L, Matlaf L, Bezrookove V, Harkins L, Martinez R, Greene M, et al. Human cytomegalovirus US28 found in glioblastoma promotes an invasive and angiogenic phenotype. Cancer Res (2011) 71(21):6643–53. doi:10.1158/0008-5472.CAN-11-0744 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 78. Xiao Y, Ye Y, Yearsley K, Jones S, Barsky SH. The lymphovascular embolus of inflammatory breast cancer expresses a stem cell-like phenotype. Am J Pathol (2008) 173(2):561–74. doi:10.2353/ajpath.2008.071214 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 79. Palangie T, Mosseri V, Mihura J, Campana F, Beuzeboc P, Dorval T, et al. Prognostic factors in inflammatory breast cancer and therapeutic implications. Eur J Cancer (1994) 30A(7):921–7. doi:10.1016/0959-8049(94)90115-5 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 80. Streblow DN, Vomaske J, Smith P, Melnychuk R, Hall L, Pancheva D, et al. Human cytomegalovirus chemokine receptor US28-induced smooth muscle cell migration is mediated by focal adhesion kinase and Src. J Biol Chem (2003) 278(50):50456–65. doi:10.1074/jbc.M307936200 Pubmed Abstract | Pubmed Full Text | CrossRef Full Text 81. Michaelis M, Doerr HW, Cinatl J. The story of human cytomegalovirus and cancer: increasing evidence and open questions. Neoplasia (2009) 11(1):1–9.