Biología e inmunopatogénesis del carcinoma espinocelular y el basocelular

-A A +A
Artículo de revisión
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 159-168

Biología e inmunopatogénesis del carcinoma espinocelular y el basocelular

Biology and immunopathogenesis of skin cancer
Autor(es): 
Ana María Mejía
aname93@hotmail.com
Médica, residente de primer año, Sección de Dermatología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia
Margarita María Velásquez
Médica dermatóloga; profesora, Sección de Dermatología, Grupo de Investigación Dermatológica, CIDERM, Universidad de Antioquia, Medellín, Colombia.
Resumen: 

El cáncer de piel es el tipo de cáncer más frecuente. El cáncer de piel no melanoma incluye el carcinoma basocelular y el carcinoma espinocelular. Debido a que la mayoría son poco agresivos y a que algunos se resecan sin estudio histopatológico, existe un subregistro. Esta revisión se enfoca en los aspectos más importantes de la biología y la inmunopatogénesis del carcinoma basocelular y del espinocelular.

Los factores de riesgo incluyen la exposición a los rayos ultravioleta, los fototipos 1 y 2, tener el cabello y los ojos claros, la ascendencia europea y el vivir en aéreas tropicales, entre otros. La patogénesis es compleja e involucra varias vías, entre las cuales están la apoptosis, las alteraciones del gen p53, las especies reactivas del oxígeno, el virus del papiloma humano, la inmunosupresión externa (medicamentos inmunosupresores) y la ocasionada por el sol.

Palabras clave: 
carcinoma de piel tipo no melanoma, Carcinoma Basocelular, carcinoma espinocelular, apoptosis, vía hedgehog (o vía para activación de factores y transcripción hedgehog).

Summary: 

Skin cancer is the most common type of cancer. The non-melanoma skin cancer includes  basal cell  carcinoma  and  squamous cell carcinoma. Since  most  of them are not aggressive and some are resected without any histopathological study, there is underreporting. This review focuses on the most important aspects
of the biology and immunopathogenesis of basal cell and squamous cell carcinoma.

Risk factors include exposure to ultraviolet rays, skin type 1 and 2, having light eyes and hair, European descent and living in tropical areas, among others. The
pathogenesis is complex and involves different routes such as apoptosis, gene p53 alterations, reactive oxygen species, human papilloma virus, external immunosuppresion (immunosuppressive drugs) and that caused by sun exposure.

Key words: 
Non-melanoma skin cancers, basal-cell carcinoma, squamouscell carcinoma, apoptosis, hedgehog pathway
PDF del articulo

Referencias

  1. Madan V, Lear JT, Szeimies R-M. Non-melanoma skin cancer. The Lancet. 2010;375:673–85.
  2. Albert MR, Weinstock M a. Keratinocyte Carcinoma. CA: A Cancer Journal for Clinicians. 2003 Sep;53:292–302.
  3. Gutierrez R. Cáncer de piel. facultad de medinicina UNAM. 2003;46:165–71.
  4. Erb P, Ji J, Wernli M, Kump E, Glaser A, Büchner S A. Role of apoptosis in basal cell and squamous cell carcinoma formation. Immunology letters. 2005;100:68–72.
  5. Cohen JL. Acinic Keratosis Treatment as a Key Component of Preventive Strategies for Nonmelanoma Skin Cancer. Dermatology. 2010;3:39–44.
  6. Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. The New England journal of medicine. 2005 Nov;353:2262–9.
  7. Tilli C.M.L.J, Van Steensel M.A. M, Krekels G.A. M, Neumann H.A. M, Ramaekers F.C.S. Molecular aetiology and pathogenesis of basal cell carcinoma. The British journal of dermatology. 2005;152:1108–24.
  8. Heal CF, Raasch B A, Buettner PG, Weedon D. Accuracy of clinical diagnosis of skin lesions. The British journal of dermatology. 2008;159:661–8.
  9. Pardo C, Murillo R, Piñeros M, Castro MA. Casos Nuevos de Cáncer en el Instituto Nacional de Cancerología, Colombia, 2002. Revista Colombiana de cancerología. 2003;7:4–19.
  10. San Clemente G.Mahecha M, Guzmán C. Enfermedades de la piel más frecuentes en consulta externa dermatológica del Hospital Universitario San Vicente de Paúl y del Hospital Infantil, Medellín,1999. Acta Medica Colombiana. 2001;26:240–4.
  11. Sanchez G, Nova J, Arias N. Prácticas frente a la radiación ultravioleta y características epidemiológicas de un grupo de pacientes con carcinoma basocelular en un centro de referencia nacional en Colombia. Revista Colombiana de Cancerología. 2010;14:144–51.
  12. Velasquez, M Zuluaga A. Primera jornada de detección precoz del cáncer de piel , Asocolderma 2011 , reporte de la experiencia en Medellín, Colombia. Revista Asociación Colombiana de Dermatología. 2012;20:135–46.
  13. Restrepo JC, Zuluaga A, Ochoa FL, Jiménez SB, Castaño OL, Uribe C, et al.. Jornada de prevención y detección de cáncer de piel en personas mayores de 18 años. Medellín, mayo de 2005. Universidad del CES. Revista CES Medellín. 2009;23:93–103.
  14. Parkin DM, Pisani P, Ferlay J. Global Cancer Statistics, 2002. CA: a cancer journal for clinicians. 1999;49: 33-64.
  15. Schulman JM, Fisher DE. Indoor UV tanning and skin cancer: helth risks and opportunities. Curr Opin Oncol . 2009;21:144–49.
  16. Meunier L. Ultraviolet light and dendritic cells. European journal of dermatology. 1999 Jun;9:269–75.
  17. Fortina AB, Piaserico S, Caforio ALP, Abeni D, Alaibac M, Angelini A, et al. Immunosuppressive level and other risk factors for basal cell carcinoma and squamous cell carcinoma in heart transplant recipients. Archives of dermatology. 2004;140:1079–85.
  18. Fitzpatrick TB, Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller SA . Carcinogenesis. Fitzpatrick’s dermatology in general medicine. Seventh Edition, Mc Graw Hill Medical,2008. 977-9
  19. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. The New England Journal of Medicine. 2001;344:975–83.
  20. Ridley AJ, Whiteside JR, McMillan TJ, Allinson SL. Cellular and sub-cellular responses to UVA in relation to carcinogenesis. International Journal of Radiation Biology. 2009;85 :177–95.
  21. Freeman SE, Hacham H, Gange RW, Maytum DJ, Sutherland JC, Sutherland BM. Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light. Proceedings of the National Academy of Sciences of the United States of America. 1989;86:5605–9.
  22. Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nature reviews. Cancer. 2008 Oct;8:743–54.
  23. Wetmore C. Sonic hedgehog in normal and neoplastic proliferation. Currenet opinion in genetics and devolpment. 2003;13:34–42.
  24. Soufir N, Gerard B, Portela M, Brice A, Liboutet M, Saiag P, et al. PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study. British journal of cancer. 2006;95:548–53.
  25. Bürglin TR. The Hedgehog protein family. Genome Biology. 2008 Jan;9:241.
  26. Tang JY, So PL, Epstein Jr. EH Novel Hedgehog pathway targets against Basal Cell Carcinoma. Toxicol Appl Pharmacol. 2007;224:257–64.
  27. Danaee H, Karagas MR, Kelsey KT, Perry AE, Nelson HH. Allelic loss at Drosophila patched gene is highly prevalent in Basal and squamous cell carcinomas of the skin. The Journal of investigative dermatology. 2006;126(5):1152–8
  28. de Zwaan SE, Haass NK. Genetics of basal cell carcinoma. The Australasian Journal of Dermatology. 2010;51:81–92; quiz 93–4.
  29. Kumar V, Abbas AK, Fausto N, Mitchell RN.The Skin Tumors. Robbins Basic Patology. 8th Edition, Elsevier 2007. 848-59
  30. Rosenstein BS, Phelps RG, Weinstock MA, Bernstein JL, Gordon ML, Rudikoff D, et al. p53 mutations in basal cell carcinomas arising in routine users of sunscreens. Photochemistry and Photobiology. 1999; 70. 798-806.
  31. Stratigos A J, Kapranos N, Petrakou E, Anastasiadou A, Pagouni A, Christofidou E, et al. Immunophenotypic analysis of the p53 gene in non-melanoma skin cancer and correlation with apoptosis and cell proliferation. Journal of the European Academy of Dermatology and Venereology : JEADV. 2005;19:180–6.
  32. Kelley KW. p 53 and the Pathogenesis of Skin Cancer. Brain, behavior, and immunity. 2008;22:629.
  33. Manestar-Blazic T, Batinac T, Hadzisejdic I, Brajac I. Apoptosis and immune response are responsible for the site-specific incidence of non-melanoma skin cáncer. Medical hypotheses. 2007;68:853–5.
  34. Kirkin V, Joos S, Zörnig M. The role of Bcl-2 family members in tumorigenesis. Biochimica Biophysica Acta. 2004;1644:229–49.
  35. Abbas AK, Lichtman AH, Sillai S. Inmunity to tumors. Cellular and molecular immunonology, 7 edition.Elsevier 2012,389-404
  36. Manestar-Blazic T, Batinac T, Hadzisejdic I, Brajac I. Apoptosis and immune response are responsible for the site-specific incidence of non-melanoma skin cancer. Medical hypotheses. 2007;68:853–5.
  37. Sjöström J, Bergh J. How apoptosis is regulated, and what goes wrong in cancer. British Medical Journal. 2001;322:1538–9.
  38. Venereo JR. Daño Oxidativo, Radicales Libres y Antioxidantes. Revista Cubana de medicina militar. 2002;31:126–33.
  39. Griffiths HR, Mistry P, Herbert KE, Lunec J. Molecular and Cellular Effect of Ultraviolet Light-Induced Genotoxicity. Critical Reviews in Clinical Laboratory Sciences. 1998;35:189–237.
  40. Euvrard S K. skin cancers in kidney and heart transplant recipients after the first squamous cell carcinoma. Transplantation. 2006;81:1093–100.
  41. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. The New England journal of medicine. 2003;348:1681–91.
  42. Dreno B. Skin cancers after transplantation. Nephrology Dialysis Transplantation. 2003;18:1052–8.
  43. Moloney FJ, Almarzouqi E, O’Kelly P, Conlon P, Murphy GM. Sunscreen use before and after transplantation and assessment of risk factors associated with skin cancer development in renal transplant recipients. Archives of dermatology. 2005;141:978–82.
  44. Tiu J, Li H, Rassekh C, Van der Sloot P, kovach R, Zhang P. Molecular basis of posttransplant squamous cell carcinoma: the potential role of cyclosporine a in carcinogenesis. The laryngoscope. 2006;106:762–9.
  45. Maddox JS, Soltani K. Risk of nonmelanoma skin cancer with azathioprine use. Inflammatory bowel diseases . 2008;14:1425–31.
  46. España A, Martínez-González M A, García-Granero M, SánchezCarpintero I, Rábago G, Herreros J. A prospective study of incident nonmelanoma skin cancer in heart transplant recipients. The Journal of investigative dermatology. 2000;115:1158–60.
  47. Caforio a L, Fortina a B, Piaserico S, Alaibac M, Tona F, Feltrin G, et al. Skin cancer in heart transplant recipients: risk factor analysis and relevance of immunosuppressive therapy. Circulation. 2000;102(19 Suppl III):III222–7.
  48. Harwood C A, McGregor JM, Proby CM, Breuer J. Human papillomavirus and the development of non-melanoma skin cancer. Journal of clinical pathology. 1999;52:249–53.
  49. Asgari MM, Kiviat NB, Critchlow CW, Stern JE, Argenyi ZB, Raugi GJ, et al. Detection of human papillomavirus DNA in cutaneous squamous cell carcinoma among immunocompetent individuals. The Journal of investigative dermatology. 2008;128:1409–17.
  50. Hashida T, Yasumoto S. Induction of chromosome abnormalities in mouse and human epidermal keratinocytes by the human papillomavirus type 16 E7 oncogene. The Journal of general virology. 1991;72:1569–77.
  51. Boukamp P. Non-melanoma skin cancer: what drives tumor development and progression? Carcinogenesis. 2005;26:1657–67.
  52. Forslund O, Ly H, Reid C, Higgins G. A broad spectrum of human papillomavirus types is present in the skin of Australian patients with non-melanoma skin cancers and solar keratosis. British journal of dermatology. 2003;149:64–73
  53. Nghiem DX, Kazimi N, Clydesdale G, Ananthaswamy HN, Kripke ML, Ullrich SE. Ultraviolet a radiation suppresses an established immune response: implications for sunscreen design. The Journal of investigative dermatology. 2001 Nov;117:1193–9.
  54. Walterscheid JP, Nghiem DX, Kazimi N, Nutt LK, Mcconkey DJ, Norval M, et al. Cis-urocanico, a sunligth-induced factor immunosuppressive, activates immune suppression via the 5-HT 2A receptor. 2006; 103:17420-25
  55. Burnet M. Concepts of autoimmune disease and their implications for therapy. Perspect Biol Med. 1967;10:14–51.
  56. Welsh MM, Karagas MR, Applebaum KM, Spencer SK, Perry AE, Nelson HH. A role for ultraviolet radiation immunosuppression in non-melanoma skin cancer as evidenced by gene-environment interactions. Carcinogenesis. 2008;29:1950–4.
  57. Byrne SN, Limón-Flores AY, Ullrich SE. Mast cell migration from the skin to the lymph nodes upon UV-irradiation reprents a key step in the induction of immune supression. The Journal of Immunology. 2008;180:4648–55.
  58. Morison WL, Bucana C, Kripke ML. Systemic suppression of contact hypersensitivity by UVB radiation is unrelated to the UVB-induced alterations in the morphology and number of Langerhans cells. Immunology. 1984;52:299–306.
Subungueal melanoma treated with local resection and free graft. ¿How to treat a patient with longitudinal melanonychia?
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 171-174
Microscopic polyangiitis
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 175-179
A 29 year-old woman with an erythematous exulcerated lesion of the forehead, resistant to treatment with sodium stibogluconate (Glucantime®)
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 122-123/192-193
Atypical Spitz tumor
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 189-191
Eccrine poroma of unusual clinical presentation
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 184-186
Birt-Hogg-Dubé Syndrome
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 180-183
Biology and immunopathogenesis of skin cancer
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 159-168
Skin microbiota: The cutaneous ecosystem
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 147-158
Urticarial vasculitis descriptive study in Medellín, Colombia: Clinical, epidemiological and laboratory findings
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 135-144
Prognostic factors associated with the duration of chronic spontaneous urticaria in a Colombian population
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 124-132
A 29 year-old woman with an erythematous exulcerated lesion of the forehead, resistant to treatment with sodium stibogluconate (Glucantime®)
Rev Asoc Colomb Dermatol. 2013; 21: 2 (Abril-Junio), 122-123/192-193

PATROCINADORES PRINCIPALES

  • MEDIHEALTH
  • SESDERMA
  • MD FARMACIA MAGISTRAL
  • EPIDERMIQUE
  • ISDIN
  • GALDERMA