Current Problems in Cancer
Volume 34, Issue 1 , Pages 14-37 , January 2010

The Etiology and Epidemiology of Merkel Cell Carcinoma

  • Maria Agelli, MD, MS, FACPM

      Affiliations

    • Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Bethesda, Maryland
    • ,
  • Limin X. Clegg, PhD, MS

      Affiliations

    • US Department of Veteran Affairs, Office of the Inspector General, Washington, DC
    • ,
  • Jürgen C. Becker, MD, PhD

      Affiliations

    • Department of Dermatology and Dermato-Oncology, University Clinic of Würzburg, Julius-Maximilians University, Würzburg, Germany
    • ,
  • Dana E. Rollison, PhD

      Affiliations

    • Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

References 

  1. Agelli M, Clegg LX. Epidemiology of primary Merkel cell carcinoma in the United States. J Am Acad Dermatol. 2003;49:832–841
  2. Toker C. Trabecular carcinoma of the skin. Arch Dermatol. 1972;105:107–110
  3. Tang CK, Toker C. Trabecular carcinoma of the skin: an ultrastructural study. Cancer. 1978;42:2311–2321
  4. Merkel F. Tastzellen and Tastkoerperchen bei Den Hausthieren und beim Menschen. Arch Mikrosc J Anat. 1875;11:636–652
  5. Halata Z, Grim M, Bauman KI. Friedrich Sigmund Merkel and his “Merkel cell”, morphology, development, and physiology: review and new results. Anat Rec A Discov Mol Cell Evol Biol. 2003;271:225–239
  6. Haag ML, Glass LF, Fenske NA. Merkel cell carcinoma (Diagnosis and treatment). Dermatol Surg. 1995;21:669–683
  7. Youker SR. Merkel cell carcinoma. Adv Dermatol. 2003;19:185–205
  8. Hewitt JB, Sherif A, Kerr KM, Stankler L. Merkel cell and squamous cell carcinomas arising in erythema ab igne. Br J Dermatol. 1993;128:591–592
  9. Agelli M, Clegg LX. Etiology and epidemiology of Merkel cell carcinoma. In: Sondak VK, Messina JL, Zager JS, et al., editors. Merkel cell carcinoma: a multidisciplinary approach. London, UK: Imperial College Press. (in press).
  10. Dinh V, Feun L, Elgart G, Savaraj N. Merkel cell carcinomas. Hematol Oncol Clin North Am. 2007;21(3):527–544
  11. Szeder V, Grim M, Halata Z, Sieber-Blum M. Neural crest origin of mammalian Merkel cells. Dev Biol. 2003;253:258–263
  12. Hitchcock CL, Bland KI, Laney RG, Franzini D, Harris B, Copeland EM. Neuroendocrine (Merkel cell) carcinoma of the skin (Its natural history, diagnosis, and treatment). Ann Surg. 1988;207:201–207
  13. Wolff-Peeters C, Marien K, Mebis J, Desmet V. A cutaneous APUDoma or Merkel cell tumor?A morphologically recognizable tumor with a biological and histological malignant aspect in contrast with its clinical behavior. Cancer. 1980;46:1810–1816
  14. Dadzie O, Teixeira F. What can primary cutaneous neuroendocrine carcinomas with squamoid and neuroendocrine differentiation teach us about the origin of Merkel cells?. Int J Dermatol. 2009;48:91–93
  15. Panelos J, Batistatou A, Paglierani M, Zioga A, Maio V, Santi R, et al. Expression of Notch-1 and alteration of the E-cadherin/beta-catenin cell adhesion complex are observed in primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma). Mod Pathol. 2009;22:959–968
  16. Satter EK, Derienzo DP. Synchronous onset of multiple cutaneous neuroendocrine (Merkel cell) carcinomas localized to the scalp. J Cutan Pathol. 2008;35:685–691
  17. Shipkov CD, Dumollard JM, Mojallal A, Seguin P. Merkel cell carcinoma vs. basal cell carcinoma: histopathologic challenges. J Cutan Pathol. 2008;35:789–790
  18. Brenner B, Katz A, Rakowski E, Feinmesser M, Bar HM, Sulkes A, et al. Merkel cell carcinoma in Israel. Isr J Med Sci. 1996;32:1235–1238
  19. Chuang TY, Su WP, Muller SA. Incidence of cutaneous T cell lymphoma and other rare skin cancers in a defined population. J Am Acad Dermatol. 1990;23(2 Pt. 1):254–256
  20. Miller RW, Rabkin CS. Merkel cell carcinoma and melanoma: etiological similarities and differences. Cancer Epidemiol Biomarkers Prev. 1999;8:153–158
  21. Riou-Gotta MO, Fournier E, Danzon A, Pelletier F, Levang J, Mermet I, et al. Rare skin cancer: a population-based cancer registry descriptive study of 151 consecutive cases diagnosed between 1980 and 2004. Acta Oncol. 2009;48:605–609
  22. Vilar-Coromina N, Perez BF, Alsina MM, Vilardell GL, Izquierdo FA, Marcos-Gragera R. [Merkel cell cancer of the skin: population-based incidence and survival, 1995-2005]. Med Clin (Barc). 2009;132:701–703
  23. Rollison DE, Becker JC. Association between Merkel cell polyomavirus and Merkel cell carcinoma. In: Sondak VK, Messina JL, Zager JS, et al., editors. merkel cell carcinoma: a multidisciplinary approach. London, UK: Imperial College Press, (in press).
  24. Hankey BF, Ries LA, Edwards BK. The surveillance, epidemiology, and end results program: a national resource. Cancer Epidemiol Biomarkers Prev. 1999;8:1117–1121
  25. Available at. http://seer.cancer.gov/Accessed on March 1, 2010.
  26. International classification of diseases for oncology. 2nd edition. Geneva, Switzerland: World Health Organization; 1990;
  27. Percy C, Von Hollen V. International classification of diseases for oncology. Field trial edition. Bethesda, Maryland: National Cancer Institute; 1986;
  28. Moll R, Lowe A, Laufer J, Franke WW. Cytokeratin 20 in human carcinomas (A new histodiagnostic marker detected by monoclonal antibodies). Am J Pathol. 1992;140:427–447
  29. Gu J, Polak JM, Van Noorden S, Pearse AG, Marangos PJ, Azzopardi JG. Immunostaining of neuron-specific enolase as a diagnostic tool for Merkel cell tumors. Cancer. 1983;52:1039–1043
  30. Warner TF, Uno H, Hafez GR, Burgess J, Bolles C, Lloyd RV, et al. Merkel cells and Merkel cell tumors (Ultrastructure, immunocytochemistry and review of the literature). Cancer. 1983;52:238–245
  31. Wick MR, Scheithauer BW, Kovacs K. Neuron-specific enolase in neuroendocrine tumors of the thymus, bronchus, and skin. Am J Clin Pathol. 1983;79:703–707
  32. Scotto J, Fears TR, Fraumeni JF. Solar radiation. In:  Schottenfeld DD,  Fraumeni JF editor. Cancer epidemiology and prevention. New York: Oxford University Press; 1996;p. 355–372
  33. Yom SS, Rosenthal DI, El Naggar AK, Kies MS, Hessel AC. Merkel cell carcinoma of the tongue and head and neck oral mucosal sites. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:761–768
  34. Allen PJ, Zhang ZF, Coit DG. Surgical management of Merkel cell carcinoma. Ann Surg. 1999;229:97–105
  35. Goessling W, McKee PH, Mayer RJ. Merkel cell carcinoma. J Clin Oncol. 2002;20:588–598
  36. Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Penas PF, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol. 2008;58:375–381
  37. Skelton HG, Smith KJ, Hitchcock CL, McCarthy WF, Lupton GP, Graham JH. Merkel cell carcinoma: analysis of clinical, histologic, and immunohistologic features of 132 cases with relation to survival. J Am Acad Dermatol. 1997;37(5 Pt. 1):734–739
  38. Bajetta E, Celio L, Platania M, Lo VS, Patuzzo R, Maurichi A, et al. Single-institution series of early-stage Merkel cell carcinoma: long-term outcomes in 95 patients managed with surgery alone. Ann Surg Oncol. 2009;16:2985–2993
  39. Weeraratna AT. Molecular profiling and genomic analysis in Merkel cell carcinoma. In: Sondak VK, Messina JL, Zager JS, DeConti RC, editors. Merkel cell carcinoma: A Multidisciplinary Approach. London, UK: Imperial College Press. (in press).
  40. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319:1096–1100
  41. Gooptu C, Woollons A, Ross J, Price M, Wojnarowska F, Morris PJ, et al. Merkel cell carcinoma arising after therapeutic immunosuppression. Br J Dermatol. 1997;137:637–641
  42. Lentz SR, Krewson L, Zutter MM. Recurrent neuroendocrine (Merkel cell) carcinoma of the skin presenting as marrow failure in a man with systemic lupus erythematosus. Med Pediatr Oncol. 1993;21:137–141
  43. Nemoto I, Sato-Matsumura KC, Fujita Y, Natsuga K, Ujiie H, Tomita Y, et al. Leukaemic dissemination of Merkel cell carcinoma in a patient with systemic lupus erythematosus. Clin Exp Dermatol. 2008;33:270–272
  44. McLoone NM, McKenna K, Edgar D, Walsh M, Bingham A. Merkel cell carcinoma in a patient with chronic sarcoidosis. Clin Exp Dermatol. 2005;30:580–582
  45. Lillis J, Ceilley RI, Nelson P. Merkel cell carcinoma in a patient with autoimmune hepatitis. J Drugs Dermatol. 2005;4:357–359
  46. Satolli F, Venturi C, Vescovi V, Morrone P, De Panfilis G. Merkel-cell carcinoma in Behcet's disease. Acta Derm Venereol. 2005;85:79
  47. Gianfreda M, Caiffi S, De Franceschi T, Dodero C, Durante R, Faletti P, et al. Merkel cell carcinoma of the skin in a patient with myasthenia gravis. Minerva Med. 2002;93:219–222
  48. Cohen Y, Amir G, Polliack A. Development and rapid dissemination of Merkel-cell carcinomatosis following therapy with fludarabine and rituximab for relapsing follicular lymphoma. Eur J Haematol. 2002;68:117–119
  49. Stone JH, Holbrook JT, Marriott MA, Tibbs AK, Sejismundo LP, Min YI, et al. Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial. Arthritis Rheum. 2006;54:608–618
  50. Wirges ML, Saporito F, Smith J. Rapid growth of Merkel cell carcinoma after treatment with rituximab. J Drugs Dermatol. 2006;5:180–181
  51. Friedlaender MM, Rubinger D, Rosenbaum E, Amir G, Siguencia E. Temporary regression of Merkel cell carcinoma metastases after cessation of cyclosporine. Transplantation. 2002;73:1849–1850
  52. Muirhead R, Ritchie DM. Partial regression of Merkel cell carcinoma in response to withdrawal of azathioprine in an immunosuppression-induced case of metastatic Merkel cell carcinoma. Clin Oncol (R Coll Radiol). 2007;19:96
  53. Bajetta E, Platania M, Catena L, Bichisao E, Fabbri A, Procopio G, et al. Merkel cell carcinoma after liver transplantation: a case report. Tumori. 2007;93:323–326
  54. Bensaleh H, Perney P, Dereure O, Guilhou JJ, Guillot B. Merkel cell carcinoma in a liver transplant patient. Am J Clin Dermatol. 2007;8:239–241
  55. Bordea C, Wojnarowska F, Millard PR, Doll H, Welsh K, Morris PJ. Skin cancers in renal-transplant recipients occur more frequently than previously recognized in a temperate climate. Transplantation. 2004;77:574–579
  56. Gilaberte M, Pujol RM, Sierra J, Matias-Guiu X, Isern J, Serret P, et al. Merkel cell carcinoma developing after bone marrow transplantation. Dermatology. 2000;201:80–82
  57. Maksymiuk B, Wygoda A, Zakliczynski M, Palen P. Primary undifferentiated small cell carcinoma (Merkel cell carcinoma) in a patient after heart transplantation—case report. Pol J Pathol. 2002;53:177–180
  58. Urbatsch A, Sams WM, Urist MM, Sturdivant R. Merkel cell carcinoma occurring in renal transplant patients. J Am Acad Dermatol. 1999;41(2 Pt. 2):289–291
  59. Penn I, First MR. Merkel's cell carcinoma in organ recipients: report of 41 cases. Transplantation. 1999;68:1717–1721
  60. Buell JF, Trofe J, Hanaway MJ, Beebe TM, Gross TG, Alloway RR, et al. Immunosuppression and Merkel cell cancer. Transplant Proc. 2002;34:1780–1781
  61. Engels EA, Frisch M, Goedert JJ, Biggar RJ, Miller RW. Merkel cell carcinoma and HIV infection. Lancet. 2002;359:497–498
  62. Burack J, Altschuler EL. Sustained remission of metastatic Merkel cell carcinoma with treatment of HIV infection. J R Soc Med. 2003;96:238–239
  63. Silva EG, Mackay B, Goepfert H, Burgess MA, Fields RS. Endocrine carcinoma of the skin (Merkel cell carcinoma). Pathol Annu. 1984;19(Pt 2):1–30
  64. Ziprin P, Smith S, Salerno G, Rosin RD. Two cases of Merkel cell tumour arising in patients with chronic lymphocytic leukaemia. Br J Dermatol. 2000;142:525–528
  65. Cerroni L, Kerl H. Primary cutaneous neuroendocrine (Merkel cell) carcinoma in association with squamous- and basal-cell carcinoma. Am J Dermatopathol. 1997;19:610–613
  66. Gomez LG, DiMaio S, Silva EG, Mackay B. Association between neuroendocrine (Merkel cell) carcinoma and squamous carcinoma of the skin. Am J Surg Pathol. 1983;7:171–177
  67. Iacocca MV, Abernethy JL, Stefanato CM, Allan AE, Bhawan J. Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin. J Am Acad Dermatol. 1998;39(5 Pt 2):882–887
  68. Jones CS, Tyring SK, Lee PC, Fine JD. Development of neuroendocrine (Merkel cell) carcinoma mixed with squamous cell carcinoma in erythema ab igne. Arch Dermatol. 1988;124:110–113
  69. Walsh NM. Primary neuroendocrine (Merkel cell) carcinoma of the skin: morphologic diversity and implications thereof. Hum Pathol. 2001;32:680–689
  70. Boukamp P. UV-induced skin cancer: similarities—variations. J Dtsch Dermatol Ges. 2005;3:493–503
  71. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003;348:1681–1691
  72. Popp S, Waltering S, Herbst C, Moll I, Boukamp P. UV–B-type mutations and chromosomal imbalances indicate common pathways for the development of Merkel and skin squamous cell carcinomas. Int J Cancer. 2002;99:352–360
  73. Brenner B, Sulkes A, Rakowsky E, Feinmesser M, Yukelson A, Bar-Haim E, et al. Second neoplasms in patients with Merkel cell carcinoma. Cancer. 2001;91:1358–1362
  74. Howard RA, Dores GM, Curtis RE, Anderson WF, Travis LB. Merkel cell carcinoma and multiple primary cancers. Cancer Epidemiol Biomarkers Prev. 2006;15:1545–1549
  75. Lardy F, Gautier C, Etesse-Pichon S, Martin JC, Demeaux H, Geniaux M, et al. [Post-radiotherapy cutaneous neuro-endocrine carcinoma]. Ann Dermatol Venereol. 1996;123:464–467
  76. Tuneu A, Pujol RM, Moreno A, Barnadas MA, de Moragas JM. Postirradiation Merkel cell carcinoma. J Am Acad Dermatol. 1989;20:505–507
  77. Andea AA, Coit DG, Amin B, Busam KJ. Merkel cell carcinoma: histologic features and prognosis. Cancer. 2008;113:2549–2558
  78. Aydin A, Kocer NE, Bekerecioglu M, Sari I. Cutaneous undifferentiated small (Merkel) cell carcinoma, that developed synchronously with multiple actinic keratoses, squamous cell carcinomas and basal cell carcinoma. J Dermatol. 2003;30:241–244
  79. Forman SB, Vidmar DA, Ferringer TC. Collision tumor composed of Merkel cell carcinoma and lentigo maligna melanoma. J Cutan Pathol. 2008;35:203–206
  80. Whiteman DC, Bray CA, Siskind V, Green AC, Hole DJ, Mackie RM. Changes in the incidence of cutaneous melanoma in the west of Scotland and Queensland, Australia: hope for health promotion?. Eur J Cancer Prev. 2008;17:243–250
  81. Van GM, Kaghad M, Leonard JH, Van RN, Naeyaert JM, Geerts ML, et al. Mutation analysis of P73 and TP53 in Merkel cell carcinoma. Br J Cancer. 2000;82:823–826
  82. Brash DE. Sunlight and the onset of skin cancer. Trends Genet. 1997;13:410–414
  83. Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A. 1991;88:10124–10128
  84. Brash DE. Roles of the transcription factor p53 in keratinocyte carcinomas. Br J Dermatol. 2006;154(Suppl 1):8–10
  85. Ziegler A, Jonason AS, Leffell DJ, Simon JA, Sharma HW, Kimmelman J, et al. Sunburn and p53 in the onset of skin cancer. Nature. 1994;372:773–776
  86. Kripke ML, Fisher MS. Immunologic parameters of ultraviolet carcinogenesis. J Natl Cancer Inst. 1976;57:211–215
  87. Greene MI, Sy MS, Kripke M, Benacerraf B. Impairment of antigen-presenting cell function by ultraviolet radiation. Proc Natl Acad Sci U S A. 1979;76:6591–6595
  88. Cooper KD, Oberhelman L, Hamilton TA, Baadsgaard O, Terhune M, LeVee G, et al. UV exposure reduces immunization rates and promotes tolerance to epicutaneous antigens in humans: relationship to dose, CD1a−DR+ epidermal macrophage induction, and Langerhans cell depletion. Proc Natl Acad Sci U S A. 1992;89:8497–8501
  89. Meunier L, Bata-Csorgo Z, Cooper KD. In human dermis, ultraviolet radiation induces expansion of a CD36+ CD11b+ CD1− macrophage subset by infiltration and proliferation; CD1+ langerhans-like dendritic antigen-presenting cells are concomitantly depleted. J Invest Dermatol. 1995;105:782–788
  90. Kolgen W, Both H, van Weelden H, Guikers KL, Bruijnzeel-Koomen CA, Knol EF, et al. Epidermal langerhans cell depletion after artificial ultraviolet B irradiation of human skin in vivo: apoptosis versus migration. J Invest Dermatol. 2002;118:812–817
  91. de Gruijl FR. Photocarcinogenesis: UVA vs. UVB radiation. Methods Enzymol. 2002;319:359–366
  92. Lunder EJ, Stern RS. Merkel-cell carcinomas in patients treated with methoxsalen and ultraviolet A radiation. N Engl J Med. 1998;339:1247–1248
  93. Tseng WP, Chu HM, How SW, Fong JM, Lin CS, Yeh S. Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Natl Cancer Inst. 1968;40:453–463
  94. Ho SY, Tsai YC, Lee MC, Guo HR. Merkel cell carcinoma in patients with long-term ingestion of arsenic. J Occup Health. 2005;47:188–192
  95. Liu SX, Davidson MM, Tang X, Walker WF, Athar M, Ivanov V, et al. Mitochondrial damage mediates genotoxicity of arsenic in mammalian cells. Cancer Res. 2005;65:3236–3242
  96. Huang HP, Huang AH, Lee JY. Merkel cell carcinoma: report of three cases. J Formos Med Assoc. 1991;90:900–903
  97. Tsuruta D, Hamada T, Mochida K, Nakagawa K, Kobayashi H, Ishii M. Merkel cell carcinoma, Bowen's disease and chronic occupational arsenic poisoning. Br J Dermatol. 1998;139:291–294
  98. Aw D, Silva AB, Palmer DB. Immunosenescence: emerging challenges for an ageing population. Immunology. 2007;120:435–446
  99. Butcher SK, Lord JM. Stress responses and innate immunity: aging as a contributory factor. Aging Cell. 2004;3:151–160
  100. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging (An evolutionary perspective on immunosenescence). Ann N Y Acad Sci. 2000;908:244–254
  101. Caruso C, Buffa S, Candore G, Colonna-Romano G, Dunn-Walters D, Kipling D, et al. Mechanisms of immunosenescence. Immun Ageing. 2009;6:10
  102. Shah KV. Human polyomavirus BKV and renal disease. Nephrol Dial Transplant. 2000;15:754–755
  103. Major EO, Mourrain P, Cummins C. JC virus-induced owl monkey glioblastoma cells in culture: biological properties associated with the viral early gene product. Virology. 1984;136:359–367
  104. Shah KV, Daniel RW, Strandberg JD. Sarcoma in a hamster inoculated with BK virus, a human papovavirus. J Natl Cancer Inst. 1975;54:945–950
  105. Zur HH. Novel human polyomaviruses—re-emergence of a well known virus family as possible human carcinogens. Int J Cancer. 2008;123:247–250
  106. Caracciolo V, Reiss K, Khalili K, De Falco G, Giordano A. Role of the interaction between large T antigen and Rb family members in the oncogenicity of JC virus. Oncogene. 2006;25:5294–5301
  107. Moens U, Van Ghelue M, Johannessen M. Oncogenic potentials of the human polyomavirus regulatory proteins. Cell Mol Life Sci. 2007;64:1656–1678
  108. Shah K. Polyomaviruses. In:  Fields B,  Knipe D,  Hoeley P editor. Fields viroloy. Philadelphia, PA: Lippincot-Raven; 1996;p. 2027–2043
  109. Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, et al. T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci U S A. 2008;105:16272–16277
  110. Garneski KM, Warcola AH, Feng Q, Kiviat NB, Leonard JH, Nghiem P. Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol. 2009;129:246–248
  111. Kassem A, Schopflin A, Diaz C, Weyers W, Stickeler E, Werner M, et al. Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res. 2008;68:5009–5013
  112. Becker JC, Houben R, Ugurel S, Trefzer U, Pfohler C, Schrama D. MC polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol. 2009;129:248–250
  113. Foulongne V, Kluger N, Dereure O, Brieu N, Guillot B, Segondy M. Merkel cell polyomavirus and Merkel cell carcinoma, France. Emerg Infect Dis. 2008;14:1491–1493
  114. Bhatia K, Goedert JJ, Modali R, Preiss L, Ayers LW. Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression. Int J Cancer (in press).
  115. Varga E, Kiss M, Szabo K, Kemeny L. Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas. Br J Dermatol. 2009;161:930–932
  116. Touze A, Gaitan J, Maruani A, Le BE, Doussinaud A, Clavel C, et al. Merkel cell polyomavirus strains in patients with Merkel cell carcinoma. Emerg Infect Dis. 2009;15:960–962
  117. Sastre-Garau X, Peter M, Avril MF, Laude H, Couturier J, Rozenberg F, et al. Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis. J Pathol. 2009;218:48–56
  118. Duncavage EJ, Zehnbauer BA, Pfeifer JD. Prevalence of Merkel cell polyomavirus in Merkel cell carcinoma. Mod Pathol. 2009;22:516–521
  119. Wetzels CT, Hoefnagel JG, Bakkers JM, Dijkman HB, Blokx WA, Melchers WJ. Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung. PLoS ONE. 2009;4:e4958
  120. Helmbold P, Lahtz C, Enk A, Herrmann-Trost P, Marsch WC, Kutzner H, et al. Frequent occurrence of RASSF1A promoter hypermethylation and Merkel cell polyomavirus in Merkel cell carcinoma. Mol Carcinog. 2009;48:903–909
  121. Sihto H, Kukko H, Koljonen V, Sankila R, Bohling T, Joensuu H. Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma. J Natl Cancer Inst. 2009;101:938–945
  122. Andres C, Belloni B, Puchta U, Sander CA, Flaig MJ. Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors. J Cutan Pathol (in press).
  123. Nakajima H, Takaishi M, Yamamoto M, Kamijima R, Kodama H, Tarutani M, et al. Screening of the specific polyoma virus as diagnostic and prognostic tools for Merkel cell carcinoma. J Dermatol Sci. 2009;56:211–213
  124. Loyo M, Guerrero-Preston R, Brait M, Hoque M, Chuang A, Kim M, et al. Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission. Int J Cancer (in press).
  125. Busam KJ, Jungbluth AA, Rekthman N, Coit D, Pulitzer M, Bini J, et al. Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas. Am J Surg Pathol. 2009;33:1378–1385
  126. Carter JJ, Paulson KG, Wipf GC, Miranda D, Madeleine MM, Johnson LG, et al. Association of Merkel cell polyomavirus-specific antibodies with Merkel cell carcinoma. J Natl Cancer Inst. 2009;101:1510–1522
  127. Pastrana DV, Tolstov YL, Becker JC, Moore PS, Chang Y, Buck CB. Quantitation of human seroresponsiveness to Merkel cell polyomavirus. PLoS Pathog. 2009;5:e1000578
  128. Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S, et al. Human Merkel cell polyomavirus infection II (MCV is a common human infection that can be detected by conformational capsid epitope immunoassays). Int J Cancer. 2009;125:1250–1256
  129. Kean JM, Rao S, Wang M, Garcea RL. Seroepidemiology of human polyomaviruses. PLoS Pathog. 2009;5:e1000363
  130. Franceschi C, Valensin S, Fagnoni F, Barbi C, Bonafe M. Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load. Exp Gerontol. 1999;34:911–921
  131. Franceschi C, Bonafe M, Valensin S. Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine. 2000;18:1717–1720
  132. Franceschi C, Valensin S, Bonafe M, Paolisso G, Yashin AI, Monti D, et al. The network and the remodeling theories of aging: historical background and new perspectives. Exp Gerontol. 2000;35:879–896

PII: S0147-0272(10)00013-9

doi: 10.1016/j.currproblcancer.2010.01.001

Current Problems in Cancer
Volume 34, Issue 1 , Pages 14-37 , January 2010

Article Tools

* Image Usage & Resolution