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p53 Abnormalities are rare events in neuroendocrine (Merkel cell) carcinoma of the skin

An immunohistochemical and SSCP analysis

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Abstract

The aim of the present study was to assess a possible role of the tumour suppressor genep53 in neuroendocrine (Merkel cell) carcinoma of the skin with regard to tumour development and tumour progression. p53 was investigated in a series of routinely processed Merkel cell carcinomas, with application of four different p53 antibodies (CM-l, PAb1801, D07, and PAb240) to 25 carcinomas and screening forp53 mutations of exons 4–8 by single-strand conformation polymorphism (SSCP) analysis in 9 cases. All 25 tumours in the present series showed the characteristic microscopic and immunohistochemical features of Merkel cell carcinoma of the skin. In 5 of the 25 Merkel cell carcinomas investigated 5–10% of tumour cell nuclei showed a positive p53 reaction with at least one anti-p53 antibody. A few scattered p53 positive nuclei were found in an additional 9 cases. The remaining 11 cases completely lacked p53 immunostaining. SSCP analysis of exons 4–8 revealed no significant alterations in the mobility shift of the single strand DNAs in the five cases with 5–10% p53-immunoreactive tumour nuclei or in five cases lacking p53 accumulation significant. Our results suggest that alterations of the p53 gene play only a minor part in the development or progression of Merkel cell carcinoma of the skin.

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References

  1. Allen RC, Graves G, Budowle B (1989) Polymerase chain reaction amplification products separated on rehydratable polyacrylamine gels and stained with silver. Biotechniques 7:736–744

    Google Scholar 

  2. Bankfalvi A, Navabi H, Bier B, Bäcker W, Jasani B, Schmid KW (1994) Wet autoclave pretreatment for antigen retrieval in diagnostic immunohistochemistry. J Pathol (Lond) 174:223–228

    Google Scholar 

  3. Barnes DM, Hanby AM, Gillet CE, Mohammed S, Hodgson S, Bobrow LG, Leigh IM, Purkis T, MacGeoch C, Spurr NK, Bartek J, Vojtesek B, Picksley SM, Lane DP (1992) Abnormal expression of wild type p53 protein in normal cells of a cancer family patient. Lancet 340:259–263

    Google Scholar 

  4. Bartek J, Bartkova J, Lukas J, Staskova Z, Vojtesek B, Lane DP (1993) Immunohistochemical analysis of the p53 oncoprotein on paraffin sections using a series of novel monoclonal antibodies. J Pathol (Lond) 169:27–34

    Google Scholar 

  5. Brinkschmidt C, Stolze P, Fahrenkamp AG, Hundeiker M, Fischer-Colbrie R, Böcker W, Schmid KW (1995) Immunohistochemical demonstration of chromogranin A, chromogranin B, and secretoneurin in Merkel cell carcinoma of the skin. An immunohistochemical study on 18 cases suggesting two types of Merkel cell carcinomas. Appl Immunohistochem 3:37–44

    Google Scholar 

  6. Campbell C, Quinn AG, Angus B, Farr PM, Rees JL (1993) Wavelength specific patterns of p53 induction in human skin following exposure to UV radiation. Cancer Res 53:2697–2699

    Google Scholar 

  7. Cesarman E, Inghirami G, Chadburn A, Knowles DM (1993) High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma. Am J Pathol 143:845–856

    Google Scholar 

  8. Dockhorn-Dworniczak B, Schröder S, Dantcheva R, Tötsch M, Stücker A, Brömmelkamp E, Bankfalvi A, Backer W, Schmid KW (1993) The role of p53 tumor suppressor gene in human thyroid cancer. Exp Clin Endocrinol 101:39–46

    Google Scholar 

  9. Esrig D, Spruck III CH, Nichols PW, Chaiwun B, Steven K, Groshen S, Chen C, Skinner DG, Jones PA, Cote RJ (1993) p53 nuclear protein accumulation correlates with mutatuions in the p53 gene, tumor grade, and stage in bladder cancer. Am J Pathol 143:1389–1397

    Google Scholar 

  10. Finlay CA, Hinds PW, Levine AJ (1989) The p53 protooncogene can act as a suppressor of transformation. Cell 57:1083–1093

    Google Scholar 

  11. Frigerio B, Capella C, Eusebi V, Tenti P, Azzopardi JG (1983) Merkel cell carcinoma of the skin: the structure and origin of normal Merker cells. Histopathology 7:229–249

    Google Scholar 

  12. Goldman D, Merril CR (1982) Silver staining of DNA in polyacryamide gels: linearity and effect of fragment size. Elecrophoresis 3:24–26

    Google Scholar 

  13. Gould E, Albores-Saavedra J, Dubner B, Smith W, Payne CM (1988) Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study. Am J Surg Pathol 12:768–772

    Google Scholar 

  14. Hall PA, Lane DP (1994) p53 in tumour pathology: can we trust immunohistochemistry? — Revisited! J Pathol (Lond) 172:1–4

    Google Scholar 

  15. Heenan PJ, Cole JM, Spagnolo DV (1990) Primary cutaneous neuroendocrine carcinoma (Merkel cell tumour). An adnexal epithelial neoplasm. Am J Dermatopathol 12:7–16

    Google Scholar 

  16. Iggo R, Gatter K, Bartek J (1990) Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 335:675–679

    Google Scholar 

  17. Lane DP (1992) p53, guardian of the genome. Nature 358:15–16

    Google Scholar 

  18. Lane DP, Crawford LV (1979) T antigen is bound to a hose protein in SV40-transformed cells. Nature 278:261–263

    Google Scholar 

  19. Lehman TA, Bennett WP, Metcalf RA, Welsh JA, Ecker J, Modali RV (1991) p53 mutations, ras mutations and p53-hea shock protein complexes. Cancer Res 51:4090–4096

    Google Scholar 

  20. Levine AJ, Momand J, Finley CA (1991) The p53 tumor suppressor gene. Nature 351:453–456

    Google Scholar 

  21. Lohmann DR, Fesseler B, Putz B, Reich U, Böhm J, Prauer H, Wunsch PH, Höfler H (1993) Infrequent mutations of the p53 gene in pulmonary carcinoid tumours. Cancer Res 53:5797–5801

    Google Scholar 

  22. Lohmann D, Putz B, Reich U, Böhm J, Prauer H, Höfler F (1993) Mutational spectrum of the p53 gene in human small cell lung cancer and relationship to clinicopathological data. Am J Pathol 142:907–915

    Google Scholar 

  23. Lohmann DR, Funk A, Niedermeyer HP, Häupel S, Höfler H (1993) Identification of p53 gene mutations in gastrointestinal and pancreatic carcinoids by nonradioisotopic SSCA. Virchows Arch [B] 64:293–296

    Google Scholar 

  24. Maniatis D, Fritsch J, Sambrook J (1992) Molecular cloning: a laboratory manual. Cold Spring Harbor Press, Cold Spring Harbor, NY

    Google Scholar 

  25. Martinez J, Hinds PW, Levine AJ (1991) Cellular localization and cell cycle regulation by a temperature sensitive p53 protein. Genes Dev 5:151–159

    Google Scholar 

  26. Moll R, Löwe A, Laufer J, Franke WW (1992) Cytokeratin 20 in human carcinoma. A new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol 140:427–447

    Google Scholar 

  27. Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53 mediated transactivation. Cell 69:1237–1245

    Google Scholar 

  28. Morgan JM, Navabi H, Schmid KW, Jasani B (1994) Possible role of tissue bound calcium ions in citrate mediated high temperature antigen retrieval. J Pathol (Lond) 174:301–307

    Google Scholar 

  29. Ofner D, Maier H, Riedmann B, Holzberger P, Nogler M, Tötsch M, Bankfalvi A, Winde G, Böcker W, Schmid KW (1995) Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in colorectal adenocarcinoma — clinicopathologic study of 109 consecutive cases demonstrating lack of long-term prognostic significance. J Clin Pathol Mol Pathol 48:M12-M16

    Google Scholar 

  30. Pontén F, Berne B, Ren Z-P, Nistér M, Pontén J (1995) Ultraviolet light induces expression of p53 and p21 in human skin: effect of sunscreen and constitutive p21 expression in skin appandages. J Invest Dermatol 105:402–406

    Google Scholar 

  31. Poremba C, Yandell DW, Huang Q, Little JB, Mellin W, Schmid KW, Böcker W, Dockhorn-Dworniczak B (1995) Frequency and spectrum of 53 mutations in gastric cancer — a molecular genetic and immunohistochemical study. Virchows Arch 426:447–455

    Google Scholar 

  32. Sarnow P, Ho YS, Williams J, Levine AJ (1982) Adenovirus EIB-58kD tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kD cellular protein in transformed cells. Cell 28:387–394

    Google Scholar 

  33. Schmid KW, Bankfalvi A, Mücke S, Öfner D, Riehemann K, Schröder S, Stücker A, Tötsch M, Dockhorn-Dworniczak B (1996) Possible relationship of p53 and mdm-2 oncoprotein expression in thyroid carcinoma. Endocr Pathol 7:121–130

    Google Scholar 

  34. Sibley RK, Delmer LP, Rosai J (1985) Primary neuroendocrine (Merkel cell?) carcinoma of the skin. I. A clinicopathologic and ultrastructural study of 43 cases. Am J Surg Pathol 9:95–108

    Google Scholar 

  35. Toker C (1972) Trabecular carcinoma of the skin. Arch Dermatol 105:107–110

    Google Scholar 

  36. Vojtsek B, Lane DP (1993) Regulation of p53 expression in human breast cancer cell lines. J Cell Sci 105:607–612

    Google Scholar 

  37. Wang D-G, Johnston CF, Anderson N, Sloan JM, Buchanan KD (1995) Overexpression of the tumour suppressor gene p53 is not implicated in neuroendocrine tumour carcinogenesis. J Pathol (Lond) 175:397–401

    Google Scholar 

  38. Werness BA, Levine AJ, Howley PM (1990) Association of human papillomavirus types 16 and 18 E6 proteins. Science 248:76–79

    Google Scholar 

  39. Wollina U (1990) Immunohistochemical investigations in epidermal Merkel cells — a common phenotype with eccrine sweat gland epithelium. Acta Histochem 88:47–50

    Google Scholar 

  40. Yana I, Nakamura T, Shin E, Karakawa E, Kurahashi H, Kurita Y, Kabayashi T, Mori T, Nishisho I, Takai S (1993) Inactivation of the p53 gene is not required for tumorigenesis of medullary thyroid carcinoma or pheochromocytoma. Jpn J Cancer Res 83:1113–1116

    Google Scholar 

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Correspondence to Kurt W. Schmid.

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Schmid, M., Janβen, K., Dockhorn-Dworniczak, B. et al. p53 Abnormalities are rare events in neuroendocrine (Merkel cell) carcinoma of the skin. Virchows Archiv 430, 233–237 (1997). https://doi.org/10.1007/BF01324807

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  • DOI: https://doi.org/10.1007/BF01324807

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