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p53 Oncoprotein Expression in Cutaneous Lymphoproliferations

p53 Oncoprotein Expression in Cutaneous Lymphoproliferations Abstract Background and Design: p53 overexpression has been reported in systemic lymphoproliferations, but our study is the first large series, to our knowledge, dealing with p53 expression in primary cutaneous lymphomas. p53 immunohistochemical detection using DO7 monoclonal antibody was performed in 54 cutaneous lymphoproliferative disorders, including 37 primary cutaneous T- or B-cell lymphomas. Results: No expression of p53 was found in 14 mycosis fungoides and seven pleomorphic T-cell lymphomas of either low or high grade of malignancy. Furthermore, no p53-positive cells were shown in low-grade B-cell lymphomas and in benign chronic dermatoses. p53 overexpression was seen over lymphomatous cells in 10 cutaneous lymphomas of high grade of Tor B-cell origin with two immunoblastic, three centroblastic, and five anaplastic lymphomas. Five of them occurred in human immunodeficiency virus—infected individuals, suggesting a possible interaction between p53 and viral proteins. p53 immunoreactivity was found over Reed-Sternberg—like cells in two cases of lymphomatoid papulosis. A labeling of keratinocytes located mainly in basal cell layers of the epidermis was observed in only five cases regardless of the lymphoma histologic subtype. Conclusions: p53 overexpression was not found in the most frequent primary cutaneous lymphomas, epidermotropic T-cell lymphomas. Alternatively, p53 immunoreactivity was observed in most primary cutaneous lymphomas of high grade of malignancy occurring in individuals either infected or not infected by human immunodeficiency virus. Molecular studies will determine if p53 overexpression is associated with p53 gene alteration and help to understand the role of p53 in primary cutaneous lymphoma genesis.(Arch Dermatol. 1995;131:1019-1024) References 1. Levine AJ, Momand J, Finlay CA. The p53 tumor suppressor gene . Nature . 1991;351:453-456.Crossref 2. Vogelstein B, Kinzler KW. p53 function and dysfunction . Cell. 1992;70:523-526.Crossref 3. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers . Science. 1991;253:49-53.Crossref 4. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation . Cell. 1992;69:1237-1245.Crossref 5. Milner J, Medcalf EA. Cotranslation of activated mutant p53 with wildtype drives the wildtype p53 protein into the mutant conformation . Cell. 1991;65:765-774.Crossref 6. Said JW, Barrera R, Shintaku IP, Nakamura H, Koeffler HP. Immunohistochemical analysis of p53 expression in malignant lymphomas . Am J Pathol. 1992;141:1343-1348. 7. Gaidano G, Ballerini P, Gong JZ, et al. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia . Proc Natl Acad Sci U S A. 1991;88:5413-5417.Crossref 8. Sidransky D, Mekkelsen T, Schwechheimer K, Rosenblum M, Cavanee W, Vogelstein B. Clonal expansion of p53 mutant cells is associated with brain tumour progression . Nature. 1992;355:846-847.Crossref 9. Ichikawa A, Hotta T, Takagi N, et al. Mutations of p53 gene and their relation to disease progression in B-cell lymphoma . Blood. 1992;79:2701-2707. 10. Sander C, Yano T, Clark HM, et al. p53 mutation is associated with progression in follicular lymphomas . Blood. 1993;82:1994-2004. 11. El Rouby S, Thomas A, Costin D, et al. p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression . Blood. 1993;82:3452-3459. 12. Villuendas R, Piris MA, Sanchez-Beato M, et al. The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations . Blood. 1993;82:3151-3156. 13. Lo Coco F, Gaidano G, Louie DC, Offit K, Chaganti RSK, Dalla-Favera R. p53 mutations are associated with histologic transformation of follicular lymphoma . Blood. 1993;82:2289-2295. 14. Piris MA, Pezella F, Martinez-Montero J-C, et al. p53 an bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time . Br J Cancer. 1994; 69:337-341.Crossref 15. De Misa RF, Azana JM, Harto A, Bellas C. p53 protein expression in cutaneous T-cell lymphoma . J Dermatol Sci. 1993;5:212-213.Crossref 16. Urano Y, Oura H, Sakaki A, et al. Immunohistological analysis of p53 expression in human skin tumors . J Dermatol Sci. 1992;4:69-75.Crossref 17. Garatti SA, Roscetti E, Trecca D, Caputo R, Neri N. Analysis of Bcl-1 locus and p53 gene in cutaneous lymphomas . J Invest Dermatol. 1993;100:461. 18. De Re V, Carbone A, De Vita S, et al. p53 protein over-expression and gene abnormalities in HIV-1 related non Hodgkin's lymphomas . Int J Cancer. 1994; 56:662-667.Crossref 19. Nakamura H, Said JW, Miller CW, Koeffler HP. Mutation and protein expression of p53 in acquired immunodeficiency syndrome-related lymphomas . Blood. 1993;82:920-926. 20. Labouyrie E, Merlio J-P, Beylot-Barry M, et al. Human immunodeficiency virus type 1 replication within cystic lymphoepithelial lesion of the salivary gland . Am J Clin Pathol. 1993;100:41-46. 21. Kerl H, Cerroni L, Burg G. The morphologic spectrum of T-cell lymphomas of the skin: a proposal for a new classification . Semin Diagn Pathol. 1991;8:55-61. 22. Baas IO, Mulder J-WR, Offerhaus GJA, Vogelstein B, Hamilton SR. An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms . J Pathol. 1994;172:5-12.Crossref 23. Cheng J, Haas M. Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines . Mol Cell Biol. 1990;10:5502-5509. 24. Sakashita A, Hattori T, Miller CW, et al. Mutations of the p53 gene in adult T-cell leukemia . Blood. 1992;79:477-480. 25. Cesarman E, Chadburn A, Inghirami G, Gaidano G, Knowles DM. Structural and funcional analysis of oncognes and tumor suppressor genes in adult T-cell leukemia/lymphoma (ATLL) reveals frequent p53 mutations . Blood. 1992; 80:3205-3216. 26. Cesarman E, Inghirami G, Chadburn A, Knowles DM. High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma . Am J Pathol. 1993;143:845-856. 27. Doglioni C, Pelosio P, Mombello A, Scarpa A, Chilosi M. Immunohistochemical evidence of abnormal expression of the anti-oncogene-encoded p53 phosphoprotein in Hodgkin's disease and CD30+ anaplastic lymphomas . Hematol Pathol. 1991;5:67-73. 28. Chadburn A, Cesarman E, Jagirdar J, Subar M, Mir RN, Knowles DM. CD30 (Ki-1) positive anaplastic large cell lymphomas in individuals infected with the human immunodeficiency virus . Cancer. 1993;72:3078-3090.Crossref 29. Kadin ME. Characteristic immunologic profile of large atypical cells in lymphomatoid papulosis: possible implications for histogenesis and relationship to other diseases . Arch Dermatol. 1986;122:1388-1390.Crossref 30. Doglioni C, Pelosio P, Mombello A, Scarpa A, Chilosi M. Immunohistochemical evidence of abnormal expression of the antioncogene-encoded p53 phosphoprotein in Hodgkin's disease and CD30+ anaplastic lymphomas . Hematol Pathol. 1991;5:67-73. 31. Willemze R, Beljaards RC, Meijer CJLM. Classification of primary cutaneous T-cell lymphomas . Histopathology. 1994;24:405-415.Crossref 32. Chang H, Benchimol S, Minden MD, Messner HA. Alterations of p53 and c-myc in the clonal evolution of malignant lymphoma . Blood. 1994;83:452-459. 33. Mercer WE, Baserga R. Expression of the p53 protein during the cell cycle of human peripheral blood lymphocytes . Exp Cell Res. 1985;160:31-46.Crossref 34. Moll UM, Riou G, Levine AJ. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion . Proc Natl Acad Sci U S A. 1992;89:7262-7266.Crossref 35. Szekely L, Selivanova G, Magnusson KP, Klein G, Wiman KG. EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins . Proc Natl Acad Sci U S A. 1993;90:5455-5459.Crossref 36. Hood Edwards R, Raab-Traub N. Alterations of the p53 gene in Epstein-Barr virus-associated immunodeficiency-related lymphomas . J Virol. 1994;68:1309-1315. 37. Ballerini P, Gaidano G, Gong JZ, et al. Multiple genetic lesions in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma . Blood. 1993; 81:166-176. 38. Mc Nutts NS, Saenz-Santamaria C, Volkenandt M, Shea CR, Albino AP. Abnormalities of p53 expression in cutaneous disorders . Arch Dermatol. 1994; 130:225-232.Crossref 39. Hall PA, Mckee PH, Menage HP, Dover R, Lane DP. High level of p53 protein in UV irradiated normal skin normal skin . Oncogene. 1993;8:203-207. 40. Palefsky JM, Gonzalez J, Greenblatt RM, Ahn DK, Hollander H. Anal intraepithelial neoplasia and anal papillomavirus infection among homosexual males with group IV HIV disease . JAMA. 1990;263:2911-2916.Crossref 41. Pollanen R, Soini Y, Vahakangas K, Paako P, Lehto VP. Aberrant p53 protein expression in cervical intra-epithelial neoplasia . Histopathology. 1993;23:471-474.Crossref 42. Hupp TR, Meet DW, Midgley CA, Lane DP. Regulation of the specific DNA binding junction of p53 . Cell. 1992;71:875-886.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.1995.01690210049008
Publisher site
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Abstract

Abstract Background and Design: p53 overexpression has been reported in systemic lymphoproliferations, but our study is the first large series, to our knowledge, dealing with p53 expression in primary cutaneous lymphomas. p53 immunohistochemical detection using DO7 monoclonal antibody was performed in 54 cutaneous lymphoproliferative disorders, including 37 primary cutaneous T- or B-cell lymphomas. Results: No expression of p53 was found in 14 mycosis fungoides and seven pleomorphic T-cell lymphomas of either low or high grade of malignancy. Furthermore, no p53-positive cells were shown in low-grade B-cell lymphomas and in benign chronic dermatoses. p53 overexpression was seen over lymphomatous cells in 10 cutaneous lymphomas of high grade of Tor B-cell origin with two immunoblastic, three centroblastic, and five anaplastic lymphomas. Five of them occurred in human immunodeficiency virus—infected individuals, suggesting a possible interaction between p53 and viral proteins. p53 immunoreactivity was found over Reed-Sternberg—like cells in two cases of lymphomatoid papulosis. A labeling of keratinocytes located mainly in basal cell layers of the epidermis was observed in only five cases regardless of the lymphoma histologic subtype. Conclusions: p53 overexpression was not found in the most frequent primary cutaneous lymphomas, epidermotropic T-cell lymphomas. Alternatively, p53 immunoreactivity was observed in most primary cutaneous lymphomas of high grade of malignancy occurring in individuals either infected or not infected by human immunodeficiency virus. Molecular studies will determine if p53 overexpression is associated with p53 gene alteration and help to understand the role of p53 in primary cutaneous lymphoma genesis.(Arch Dermatol. 1995;131:1019-1024) References 1. Levine AJ, Momand J, Finlay CA. The p53 tumor suppressor gene . Nature . 1991;351:453-456.Crossref 2. Vogelstein B, Kinzler KW. p53 function and dysfunction . Cell. 1992;70:523-526.Crossref 3. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers . Science. 1991;253:49-53.Crossref 4. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation . Cell. 1992;69:1237-1245.Crossref 5. Milner J, Medcalf EA. Cotranslation of activated mutant p53 with wildtype drives the wildtype p53 protein into the mutant conformation . Cell. 1991;65:765-774.Crossref 6. Said JW, Barrera R, Shintaku IP, Nakamura H, Koeffler HP. Immunohistochemical analysis of p53 expression in malignant lymphomas . Am J Pathol. 1992;141:1343-1348. 7. Gaidano G, Ballerini P, Gong JZ, et al. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia . Proc Natl Acad Sci U S A. 1991;88:5413-5417.Crossref 8. Sidransky D, Mekkelsen T, Schwechheimer K, Rosenblum M, Cavanee W, Vogelstein B. Clonal expansion of p53 mutant cells is associated with brain tumour progression . Nature. 1992;355:846-847.Crossref 9. Ichikawa A, Hotta T, Takagi N, et al. Mutations of p53 gene and their relation to disease progression in B-cell lymphoma . Blood. 1992;79:2701-2707. 10. Sander C, Yano T, Clark HM, et al. p53 mutation is associated with progression in follicular lymphomas . Blood. 1993;82:1994-2004. 11. El Rouby S, Thomas A, Costin D, et al. p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression . Blood. 1993;82:3452-3459. 12. Villuendas R, Piris MA, Sanchez-Beato M, et al. The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations . Blood. 1993;82:3151-3156. 13. Lo Coco F, Gaidano G, Louie DC, Offit K, Chaganti RSK, Dalla-Favera R. p53 mutations are associated with histologic transformation of follicular lymphoma . Blood. 1993;82:2289-2295. 14. Piris MA, Pezella F, Martinez-Montero J-C, et al. p53 an bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time . Br J Cancer. 1994; 69:337-341.Crossref 15. De Misa RF, Azana JM, Harto A, Bellas C. p53 protein expression in cutaneous T-cell lymphoma . J Dermatol Sci. 1993;5:212-213.Crossref 16. Urano Y, Oura H, Sakaki A, et al. Immunohistological analysis of p53 expression in human skin tumors . J Dermatol Sci. 1992;4:69-75.Crossref 17. Garatti SA, Roscetti E, Trecca D, Caputo R, Neri N. Analysis of Bcl-1 locus and p53 gene in cutaneous lymphomas . J Invest Dermatol. 1993;100:461. 18. De Re V, Carbone A, De Vita S, et al. p53 protein over-expression and gene abnormalities in HIV-1 related non Hodgkin's lymphomas . Int J Cancer. 1994; 56:662-667.Crossref 19. Nakamura H, Said JW, Miller CW, Koeffler HP. Mutation and protein expression of p53 in acquired immunodeficiency syndrome-related lymphomas . Blood. 1993;82:920-926. 20. Labouyrie E, Merlio J-P, Beylot-Barry M, et al. Human immunodeficiency virus type 1 replication within cystic lymphoepithelial lesion of the salivary gland . Am J Clin Pathol. 1993;100:41-46. 21. Kerl H, Cerroni L, Burg G. The morphologic spectrum of T-cell lymphomas of the skin: a proposal for a new classification . Semin Diagn Pathol. 1991;8:55-61. 22. Baas IO, Mulder J-WR, Offerhaus GJA, Vogelstein B, Hamilton SR. An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms . J Pathol. 1994;172:5-12.Crossref 23. Cheng J, Haas M. Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines . Mol Cell Biol. 1990;10:5502-5509. 24. Sakashita A, Hattori T, Miller CW, et al. Mutations of the p53 gene in adult T-cell leukemia . Blood. 1992;79:477-480. 25. Cesarman E, Chadburn A, Inghirami G, Gaidano G, Knowles DM. Structural and funcional analysis of oncognes and tumor suppressor genes in adult T-cell leukemia/lymphoma (ATLL) reveals frequent p53 mutations . Blood. 1992; 80:3205-3216. 26. Cesarman E, Inghirami G, Chadburn A, Knowles DM. High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma . Am J Pathol. 1993;143:845-856. 27. Doglioni C, Pelosio P, Mombello A, Scarpa A, Chilosi M. Immunohistochemical evidence of abnormal expression of the anti-oncogene-encoded p53 phosphoprotein in Hodgkin's disease and CD30+ anaplastic lymphomas . Hematol Pathol. 1991;5:67-73. 28. Chadburn A, Cesarman E, Jagirdar J, Subar M, Mir RN, Knowles DM. CD30 (Ki-1) positive anaplastic large cell lymphomas in individuals infected with the human immunodeficiency virus . Cancer. 1993;72:3078-3090.Crossref 29. Kadin ME. Characteristic immunologic profile of large atypical cells in lymphomatoid papulosis: possible implications for histogenesis and relationship to other diseases . Arch Dermatol. 1986;122:1388-1390.Crossref 30. Doglioni C, Pelosio P, Mombello A, Scarpa A, Chilosi M. Immunohistochemical evidence of abnormal expression of the antioncogene-encoded p53 phosphoprotein in Hodgkin's disease and CD30+ anaplastic lymphomas . Hematol Pathol. 1991;5:67-73. 31. Willemze R, Beljaards RC, Meijer CJLM. Classification of primary cutaneous T-cell lymphomas . Histopathology. 1994;24:405-415.Crossref 32. Chang H, Benchimol S, Minden MD, Messner HA. Alterations of p53 and c-myc in the clonal evolution of malignant lymphoma . Blood. 1994;83:452-459. 33. Mercer WE, Baserga R. Expression of the p53 protein during the cell cycle of human peripheral blood lymphocytes . Exp Cell Res. 1985;160:31-46.Crossref 34. Moll UM, Riou G, Levine AJ. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion . Proc Natl Acad Sci U S A. 1992;89:7262-7266.Crossref 35. Szekely L, Selivanova G, Magnusson KP, Klein G, Wiman KG. EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins . Proc Natl Acad Sci U S A. 1993;90:5455-5459.Crossref 36. Hood Edwards R, Raab-Traub N. Alterations of the p53 gene in Epstein-Barr virus-associated immunodeficiency-related lymphomas . J Virol. 1994;68:1309-1315. 37. Ballerini P, Gaidano G, Gong JZ, et al. Multiple genetic lesions in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma . Blood. 1993; 81:166-176. 38. Mc Nutts NS, Saenz-Santamaria C, Volkenandt M, Shea CR, Albino AP. Abnormalities of p53 expression in cutaneous disorders . Arch Dermatol. 1994; 130:225-232.Crossref 39. Hall PA, Mckee PH, Menage HP, Dover R, Lane DP. High level of p53 protein in UV irradiated normal skin normal skin . Oncogene. 1993;8:203-207. 40. Palefsky JM, Gonzalez J, Greenblatt RM, Ahn DK, Hollander H. Anal intraepithelial neoplasia and anal papillomavirus infection among homosexual males with group IV HIV disease . JAMA. 1990;263:2911-2916.Crossref 41. Pollanen R, Soini Y, Vahakangas K, Paako P, Lehto VP. Aberrant p53 protein expression in cervical intra-epithelial neoplasia . Histopathology. 1993;23:471-474.Crossref 42. Hupp TR, Meet DW, Midgley CA, Lane DP. Regulation of the specific DNA binding junction of p53 . Cell. 1992;71:875-886.Crossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Sep 1, 1995

References

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