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. 1993 Dec;143(6):1667–1678.

Keratin 17 expression as a marker for epithelial transformation in viral warts.

C M Proby 1, L Churchill 1, P E Purkis 1, M T Glover 1, C J Sexton 1, I M Leigh 1
PMCID: PMC1887274  PMID: 7504888

Abstract

The profile of keratin expression in benign warts from various cutaneous and mucosal sites along with dysplastic warts and squamous cell carcinomas has been examined using a panel of monospecific antibodies to epithelial keratins. Viral warts and verrucous keratoses from immunosuppressed renal transplant recipients show a spectrum of squamous atypia from benign lesions, from minimal changes to full thickness dysplasia. Changes associated with malignancy include loss of differentiation-specific keratins 1 and 10 together with expansion of basal cell epitopes and inappropriate expression of simple epithelial keratins 8, 18, and 19 in advanced squamous cell carcinoma. This late expression of keratins 8 and 18 contrasts with early expression of keratin 17 in all dysplastic lesions examined. Keratin 17 is found suprabasally in hyperproliferative lesions, including benign warts, but marked basal plus suprabasal expression is seen increasingly in malignantly transformed epidermis. These findings were not specific to immunosuppression, as shown by identical findings in control squamous cell carcinoma from nonimmunosuppressed individuals. Keratin 17 expression may prove prognostically helpful when assessing dysplasia in epidermal tumors.

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  1. Angus B., Kiberu S., Purvis J., Wilkinson L., Horne C. H. Cytokeratins in cervical dysplasia and neoplasia: a comparative study of immunohistochemical staining using monoclonal antibodies NCL-5D3, CAM 5.2, and PKK1. J Pathol. 1988 May;155(1):71–75. doi: 10.1002/path.1711550111. [DOI] [PubMed] [Google Scholar]
  2. Bartek J., Durban E. M., Hallowes R. C., Taylor-Papadimitriou J. A subclass of luminal epithelial cells in the human mammary gland, defined by antibodies to cytokeratins. J Cell Sci. 1985 Apr;75:17–33. doi: 10.1242/jcs.75.1.17. [DOI] [PubMed] [Google Scholar]
  3. Benton E. C., McLaren K., Barr B. B., Blessing K., Bunney M. H., Rüdlinger R., Smith I. W., Hunter J. A. Human papilloma virus infection and its relationship to skin cancer in a group of renal allograft recipients. Curr Probl Dermatol. 1989;18:168–177. doi: 10.1159/000416853. [DOI] [PubMed] [Google Scholar]
  4. Blessing K., McLaren K. M., Benton E. C., Barr B. B., Bunney M. H., Smith I. W., Beveridge G. W. Histopathology of skin lesions in renal allograft recipients--an assessment of viral features and dysplasia. Histopathology. 1989 Feb;14(2):129–139. doi: 10.1111/j.1365-2559.1989.tb02123.x. [DOI] [PubMed] [Google Scholar]
  5. Bártek J., Bártková J., Taylor-Papadimitriou J., Rejthar A., Kovarík J., Lukás Z., Vojtesek B. Differential expression of keratin 19 in normal human epithelial tissues revealed by monospecific monoclonal antibodies. Histochem J. 1986 Oct;18(10):565–575. doi: 10.1007/BF01675198. [DOI] [PubMed] [Google Scholar]
  6. Bártek J., Vojtesek B., Stasková Z., Bártková J., Kerekés Z., Rejthar A., Kovarík J. A series of 14 new monoclonal antibodies to keratins: characterization and value in diagnostic histopathology. J Pathol. 1991 Jul;164(3):215–224. doi: 10.1002/path.1711640306. [DOI] [PubMed] [Google Scholar]
  7. Cooper D., Schermer A., Sun T. T. Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: strategies, applications, and limitations. Lab Invest. 1985 Mar;52(3):243–256. [PubMed] [Google Scholar]
  8. Cotsarelis G., Sun T. T., Lavker R. M. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990 Jun 29;61(7):1329–1337. doi: 10.1016/0092-8674(90)90696-c. [DOI] [PubMed] [Google Scholar]
  9. Dover R., Potten C. S. Cell cycle kinetics of cultured human epidermal keratinocytes. J Invest Dermatol. 1983 May;80(5):423–429. doi: 10.1111/1523-1747.ep12555494. [DOI] [PubMed] [Google Scholar]
  10. Favre M., Obalek S., Jablonska S., Orth G. Human papillomavirus type 49, a type isolated from flat warts of renal transplant patients. J Virol. 1989 Nov;63(11):4909–4909. doi: 10.1128/jvi.63.11.4909-.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fisher M. S., Kripke M. L. Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice. Science. 1982 Jun 4;216(4550):1133–1134. doi: 10.1126/science.6210958. [DOI] [PubMed] [Google Scholar]
  12. Fuchs E., Tyner A. L., Giudice G. J., Marchuk D., RayChaudhury A., Rosenberg M. The human keratin genes and their differential expression. Curr Top Dev Biol. 1987;22:5–34. doi: 10.1016/s0070-2153(08)60097-6. [DOI] [PubMed] [Google Scholar]
  13. Guelstein V. I., Tchypysheva T. A., Ermilova V. D., Litvinova L. V., Troyanovsky S. M., Bannikov G. A. Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer. Int J Cancer. 1988 Aug 15;42(2):147–153. doi: 10.1002/ijc.2910420202. [DOI] [PubMed] [Google Scholar]
  14. Hanto D. W., Frizzera G., Gajl-Peczalska K. J., Simmons R. L. Epstein-Barr virus, immunodeficiency, and B cell lymphoproliferation. Transplantation. 1985 May;39(5):461–472. doi: 10.1097/00007890-198505000-00001. [DOI] [PubMed] [Google Scholar]
  15. Hoxtell E. O., Mandel J. S., Murray S. S., Schuman L. M., Goltz R. W. Incidence of skin carcinoma after renal transplantation. Arch Dermatol. 1977 Apr;113(4):436–438. [PubMed] [Google Scholar]
  16. Kinlen L. J., Sheil A. G., Peto J., Doll R. Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs. Br Med J. 1979 Dec 8;2(6203):1461–1466. doi: 10.1136/bmj.2.6203.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kovarík J., Rejthar A., Lauerová L., Vojtesek B., Bártková J. Monoclonal antibodies against individual cytokeratins in the detection of metastatic spread. Int J Cancer Suppl. 1988;3:50–55. doi: 10.1002/ijc.2910410811. [DOI] [PubMed] [Google Scholar]
  18. Kripke M. L., Morison W. L. Modulation of immune function by UV radiation. J Invest Dermatol. 1985 Jul;85(1 Suppl):62s–66s. doi: 10.1111/1523-1747.ep12275479. [DOI] [PubMed] [Google Scholar]
  19. Lane E. B., Alexander C. M. Use of keratin antibodies in tumor diagnosis. Semin Cancer Biol. 1990 Jun;1(3):165–179. [PubMed] [Google Scholar]
  20. Lane E. B., Bártek J., Purkis P. E., Leigh I. M. Keratin antigens in differentiating skin. Ann N Y Acad Sci. 1985;455:241–258. doi: 10.1111/j.1749-6632.1985.tb50415.x. [DOI] [PubMed] [Google Scholar]
  21. Lane E. B. Monoclonal antibodies provide specific intramolecular markers for the study of epithelial tonofilament organization. J Cell Biol. 1982 Mar;92(3):665–673. doi: 10.1083/jcb.92.3.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lane E. B., Wilson C. A., Hughes B. R., Leigh I. M. Stem cells in hair follicles. Cytoskeletal studies. Ann N Y Acad Sci. 1991 Dec 26;642:197–213. doi: 10.1111/j.1749-6632.1991.tb24388.x. [DOI] [PubMed] [Google Scholar]
  23. Lavker R. M., Sun T. T. Epidermal stem cells. J Invest Dermatol. 1983 Jul;81(1 Suppl):121s–127s. doi: 10.1111/1523-1747.ep12540880. [DOI] [PubMed] [Google Scholar]
  24. Lavker R. M., Sun T. T. Heterogeneity in epidermal basal keratinocytes: morphological and functional correlations. Science. 1982 Mar 5;215(4537):1239–1241. doi: 10.1126/science.7058342. [DOI] [PubMed] [Google Scholar]
  25. Leigh I. M., Purkis P. E., Whitehead P., Lane E. B. Monospecific monoclonal antibodies to keratin 1 carboxy terminal (synthetic peptide) and to keratin 10 as markers of epidermal differentiation. Br J Dermatol. 1993 Aug;129(2):110–119. doi: 10.1111/j.1365-2133.1993.tb03511.x. [DOI] [PubMed] [Google Scholar]
  26. Lindberg K., Rheinwald J. G. Suprabasal 40 kd keratin (K19) expression as an immunohistologic marker of premalignancy in oral epithelium. Am J Pathol. 1989 Jan;134(1):89–98. [PMC free article] [PubMed] [Google Scholar]
  27. Lutzner M. A., Blanchet-Bardon C., Orth G. Clinical observations, virologic studies, and treatment trials in patients with epidermodysplasia verruciformis, a disease induced by specific human papillomaviruses. J Invest Dermatol. 1984 Jul;83(1 Suppl):18s–25s. doi: 10.1111/1523-1747.ep12281128. [DOI] [PubMed] [Google Scholar]
  28. Lutzner M. A., Orth G., Dutronquay V., Ducasse M. F., Kreis H., Crosnier J. Detection of human papillomavirus type 5 DNA in skin cancers of an immunosuppressed renal allograft recipient. Lancet. 1983 Aug 20;2(8347):422–424. doi: 10.1016/s0140-6736(83)90389-6. [DOI] [PubMed] [Google Scholar]
  29. Makin C. A., Bobrow L. G., Bodmer W. F. Monoclonal antibody to cytokeratin for use in routine histopathology. J Clin Pathol. 1984 Sep;37(9):975–983. doi: 10.1136/jcp.37.9.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Markey A. C., Lane E. B., Churchill L. J., MacDonald D. M., Leigh I. M. Expression of simple epithelial keratins 8 and 18 in epidermal neoplasia. J Invest Dermatol. 1991 Nov;97(5):763–770. doi: 10.1111/1523-1747.ep12486607. [DOI] [PubMed] [Google Scholar]
  31. McKhann C. F. Primary malignancy in patients undergoing immunosuppression for renal transplantation. Transplantation. 1969 Aug;8(2):209–212. doi: 10.1097/00007890-196908000-00033. [DOI] [PubMed] [Google Scholar]
  32. Moll I., Moll R. Comparative cytokeratin analysis of sweat gland ducts and eccrine poromas. Arch Dermatol Res. 1991;283(5):300–309. doi: 10.1007/BF00376618. [DOI] [PubMed] [Google Scholar]
  33. Moll I., Troyanovsky S. M., Moll R. Special program of differentiation expressed in keratinocytes of human haarscheiben: an analysis of individual cytokeratin polypeptides. J Invest Dermatol. 1993 Jan;100(1):69–76. doi: 10.1111/1523-1747.ep12354535. [DOI] [PubMed] [Google Scholar]
  34. Moll R., Franke W. W., Schiller D. L., Geiger B., Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. doi: 10.1016/0092-8674(82)90400-7. [DOI] [PubMed] [Google Scholar]
  35. Moll R., Franke W. W., Volc-Platzer B., Krepler R. Different keratin polypeptides in epidermis and other epithelia of human skin: a specific cytokeratin of molecular weight 46,000 in epithelia of the pilosebaceous tract and basal cell epitheliomas. J Cell Biol. 1982 Oct;95(1):285–295. doi: 10.1083/jcb.95.1.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Moll R., Löwe A., Laufer J., Franke W. W. Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol. 1992 Feb;140(2):427–447. [PMC free article] [PubMed] [Google Scholar]
  37. Nagle R. B., Böcker W., Davis J. R., Heid H. W., Kaufmann M., Lucas D. O., Jarasch E. D. Characterization of breast carcinomas by two monoclonal antibodies distinguishing myoepithelial from luminal epithelial cells. J Histochem Cytochem. 1986 Jul;34(7):869–881. doi: 10.1177/34.7.2423579. [DOI] [PubMed] [Google Scholar]
  38. Ostrow R. S., Zachow K. R., Shaver M. K., Faras A. J. Human papillomavirus type 27: detection of a novel human papillomavirus in common warts of a renal transplant recipient. J Virol. 1989 Nov;63(11):4904–4904. doi: 10.1128/jvi.63.11.4904-.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Penn I. Malignancies associated with immunosuppressive or cytotoxic therapy. Surgery. 1978 May;83(5):492–502. [PubMed] [Google Scholar]
  40. Penn I. The changing pattern of posttransplant malignancies. Transplant Proc. 1991 Feb;23(1 Pt 2):1101–1103. [PubMed] [Google Scholar]
  41. Purkis P. E., Steel J. B., Mackenzie I. C., Nathrath W. B., Leigh I. M., Lane E. B. Antibody markers of basal cells in complex epithelia. J Cell Sci. 1990 Sep;97(Pt 1):39–50. doi: 10.1242/jcs.97.1.39. [DOI] [PubMed] [Google Scholar]
  42. Quinn A. G., McLelland J., Essex T., Farr P. M. Measurement of cutaneous inflammatory reactions using a scanning laser-Doppler velocimeter. Br J Dermatol. 1991 Jul;125(1):30–37. doi: 10.1111/j.1365-2133.1991.tb06035.x. [DOI] [PubMed] [Google Scholar]
  43. Raju G. C. Expression of the cytokeratin marker CAM 5.2 in cervical neoplasia. Histopathology. 1988 Apr;12(4):437–443. doi: 10.1111/j.1365-2559.1988.tb01958.x. [DOI] [PubMed] [Google Scholar]
  44. Ramaekers F., Huysmans A., Schaart G., Moesker O., Vooijs P. Tissue distribution of keratin 7 as monitored by a monoclonal antibody. Exp Cell Res. 1987 May;170(1):235–249. doi: 10.1016/0014-4827(87)90133-9. [DOI] [PubMed] [Google Scholar]
  45. Roop D. R., Huitfeldt H., Kilkenny A., Yuspa S. H. Regulated expression of differentiation-associated keratins in cultured epidermal cells detected by monospecific antibodies to unique peptides of mouse epidermal keratins. Differentiation. 1987;35(2):143–150. doi: 10.1111/j.1432-0436.1987.tb00162.x. [DOI] [PubMed] [Google Scholar]
  46. Rüdlinger R., Smith I. W., Bunney M. H., Hunter J. A. Human papillomavirus infections in a group of renal transplant recipients. Br J Dermatol. 1986 Dec;115(6):681–692. doi: 10.1111/j.1365-2133.1986.tb06649.x. [DOI] [PubMed] [Google Scholar]
  47. Schaafsma H. E., Ramaekers F. C., van Muijen G. N., Lane E. B., Leigh I. M., Robben H., Huijsmans A., Ooms E. C., Ruiter D. J. Distribution of cytokeratin polypeptides in human transitional cell carcinomas, with special emphasis on changing expression patterns during tumor progression. Am J Pathol. 1990 Feb;136(2):329–343. [PMC free article] [PubMed] [Google Scholar]
  48. Schermer A., Galvin S., Sun T. T. Differentiation-related expression of a major 64K corneal keratin in vivo and in culture suggests limbal location of corneal epithelial stem cells. J Cell Biol. 1986 Jul;103(1):49–62. doi: 10.1083/jcb.103.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Schermer A., Jester J. V., Hardy C., Milano D., Sun T. T. Transient synthesis of K6 and K16 keratins in regenerating rabbit corneal epithelium: keratin markers for an alternative pathway of keratinocyte differentiation. Differentiation. 1989 Dec;42(2):103–110. doi: 10.1111/j.1432-0436.1989.tb00611.x. [DOI] [PubMed] [Google Scholar]
  50. Sheil A. G. Cancer in renal allograft recipients in Australia and New Zealand. Transplant Proc. 1977 Mar;9(1):1133–1136. [PubMed] [Google Scholar]
  51. Smedts F., Ramaekers F., Robben H., Pruszczynski M., van Muijen G., Lane B., Leigh I., Vooijs P. Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia. Am J Pathol. 1990 Mar;136(3):657–668. [PMC free article] [PubMed] [Google Scholar]
  52. Smedts F., Ramaekers F., Troyanovsky S., Pruszczynski M., Link M., Lane B., Leigh I., Schijf C., Vooijs P. Keratin expression in cervical cancer. Am J Pathol. 1992 Aug;141(2):497–511. [PMC free article] [PubMed] [Google Scholar]
  53. Smedts F., Ramaekers F., Troyanovsky S., Pruszczynski M., Robben H., Lane B., Leigh I., Plantema F., Vooijs P. Basal-cell keratins in cervical reserve cells and a comparison to their expression in cervical intraepithelial neoplasia. Am J Pathol. 1992 Mar;140(3):601–612. [PMC free article] [PubMed] [Google Scholar]
  54. Spencer D. A. Hospital inquiries. Br Med J. 1978 Sep 16;2(6140):828–828. doi: 10.1136/bmj.2.6140.828-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Stasiak P. C., Purkis P. E., Leigh I. M., Lane E. B. Keratin 19: predicted amino acid sequence and broad tissue distribution suggest it evolved from keratinocyte keratins. J Invest Dermatol. 1989 May;92(5):707–716. doi: 10.1111/1523-1747.ep12721500. [DOI] [PubMed] [Google Scholar]
  56. Sun T. T., Green H. Cultured epithelial cells of cornea, conjunctiva and skin: absence of marked intrinsic divergence of their differentiated states. Nature. 1977 Oct 6;269(5628):489–493. doi: 10.1038/269489a0. [DOI] [PubMed] [Google Scholar]
  57. Sun T. T., Green H. Immunofluorescent staining of keratin fibers in cultured cells. Cell. 1978 Jul;14(3):469–476. doi: 10.1016/0092-8674(78)90233-7. [DOI] [PubMed] [Google Scholar]
  58. Troyanovsky S. M., Guelstein V. I., Tchipysheva T. A., Krutovskikh V. A., Bannikov G. A. Patterns of expression of keratin 17 in human epithelia: dependency on cell position. J Cell Sci. 1989 Jul;93(Pt 3):419–426. doi: 10.1242/jcs.93.3.419. [DOI] [PubMed] [Google Scholar]
  59. Van der Leest R. J., Zachow K. R., Ostrow R. S., Bender M., Pass F., Faras A. J. Human papillomavirus heterogeneity in 36 renal transplant recipients. Arch Dermatol. 1987 Mar;123(3):354–357. doi: 10.1001/archderm.123.3.354. [DOI] [PubMed] [Google Scholar]
  60. Vousden K. H. Human papillomaviruses and cervical carcinoma. Cancer Cells. 1989 Oct;1(2):43–50. [PubMed] [Google Scholar]
  61. Weiss R. A., Eichner R., Sun T. T. Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes. J Cell Biol. 1984 Apr;98(4):1397–1406. doi: 10.1083/jcb.98.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Wu Y. J., Parker L. M., Binder N. E., Beckett M. A., Sinard J. H., Griffiths C. T., Rheinwald J. G. The mesothelial keratins: a new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia. Cell. 1982 Dec;31(3 Pt 2):693–703. doi: 10.1016/0092-8674(82)90324-5. [DOI] [PubMed] [Google Scholar]
  63. van Muijen G. N., Ruiter D. J., Franke W. W., Achtstätter T., Haasnoot W. H., Ponec M., Warnaar S. O. Cell type heterogeneity of cytokeratin expression in complex epithelia and carcinomas as demonstrated by monoclonal antibodies specific for cytokeratins nos. 4 and 13. Exp Cell Res. 1986 Jan;162(1):97–113. doi: 10.1016/0014-4827(86)90429-5. [DOI] [PubMed] [Google Scholar]

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