Proliferação de antígeno de célula nuclear (PCNA), p53 e expressão de MDM2 em doença do Hodgkin
Palavras-chave:
Antígeno nuclear de célula em proliferação, Genes p53, Proteínas proto-oncogênicas c-mdm2, Doença de Hodgkin, ImunohistoquímicaResumo
CONTEXTO E OBJETIVO: As células tumorais da doença de Hodgkin (HD) são positivas para marcadores de proliferação celular que são analisados por seus genes e respectivas proteínas. A correlação entre a expressão destas proteínas e os parâmetros clínico-laboratoriais são, no momento, de importância para o prognóstico da doença. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo da expressão do antígeno de proliferação celular (PCNA) e da p53 e MDM2 em tecidos obtidos ao diagnóstico, fi xados por formol, embebidos em parafi na de 51 pacientes com HD. O trabalho foi realizado na Divisão de Hematologia e Transfusão, Hospital São Paulo, Universidade Federal de São Paulo. MÉTODOS: As expressões antigênicas foram analisadas através da proporção de células de Hodgkin e células de Reed Sternberg (HRS) e linfócitos reacionais (L) positivos. A intensidade de expressão de cada proteína foi comparada entre L e HRS através do coefi ciente de Spearman. A comparação da PCNA, p53 e MDM2 em L e HRS se fez pelo teste de Fiedman. As correlações entre variáveis clínico-laboratoriais, comprometimento da medula óssea, taxas de sobrevida geral e remissão clínica com as proteínas em HRS se fi zeram pelo coefi ciente de Pearson. RESULTADOS: Houve superexpressão das três proteínas em células HRS comparadas aos L (p < 0,001). Nas células HRS, a MDM2 foi maior que a p53 e a PCNA (p < 0,003), que foram equivalentes. Nos L, a p53 foi menor que a MDM2 e a PCNA (p < 0,001), que foram equivalentes Não houve relação entre as expressões das proteínas com as variáveis clínico-laboratoriais e sobrevida. CONCLUSÕES: PCNA, p53 e MDM2 são marcadores tumorais na HD, porém não mostraram signifi cado clínico-prognóstico em nossa análise.
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Falini B, Stein H, Pileri S, et al. Expression of lymphoid-associated antigens on Hodgkin’s and Reed-Sternberg cells of Hodgkin’s disease. An immunocytochemical study on lymph node cytospins using monoclonal antibodies. Histopathology. 1987;11(12):1229-42.
Hsu SM, Hsu PL. Aberrant expression of T cell and B-cell markers in myelocyte/monocyte/histiocyte-derived lymphoma and leukemia cells. Is the infrequent expression of T/B cell markers sufficient to establish a lymphoid origin from Hodgkin’s Reed-Sternberg cells? Am J Pathol. 1989;134(1):203-12.
Morgan KG, Quirke P, O’Brien CJ, Bird CC. Hodgkin’s disease: a flow cytometric study. J Clin Pathol. 1988;41(4):365-9.
Cossman J. Gene expression analysis of single neoplastic cells and the pathogenesis of Hodgkin’s lymphoma. J Histochem Cytochem. 2001;49(6):799-800.
Spieker T, Kurth J, Kuppers R, Rajewsky K, Bräuninger A, Hansmann ML. Molecular single-cell analysis of the clonal relationship of small Epstein-Barr virus-infected cells and Epstein-Barr virus-harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease. Blood. 2000;96(9):3133-8.
Kuppers R, Sousa AB, Baur AS, Strickler JG, Rajewsky K, Hansmann ML. Common germinal-center B-cell origin of malignant cells in two composite lymphomas, involving classical Hodgkin’s disease and either follicular lymphoma or B-CLL. Mol Med. 2001;7(5):285-92.
Stein H, Hummel M. Cellular origin and clonality of classic Hodgkin’s lymphoma: immunophenotypic and molecular studies. Semin Hematol. 1999;36(3):233-41.
Falini B, Fizzotti M, Pucciarini A, et al. A monoclonal antibody (MUM1p) detects expression of the MUM1p/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood. 2000;95(6):2084-92.
Foss HD, Reusch R, Demel G, et al. Frequent expression of the B-cell-specific activator protein in Reed-Sternberg cells of classical Hodgkin’s disease provides further evidence for its B-cell origin. Blood. 1999;94(9):3108-13.
Sabattini E, Gerdes J, Gherlinzoni F, et al. Comparison between the monoclonal antibodies Ki-67 and PC10 in 125 malignant lymphomas. J Pathol. 1993;169(4):397-403.
Garcia RL, Coltrera MD, Gown AM. Analysis of proliferative grade using anti-PCNA/cyclin monoclonal antibodies in fixed, embedded tissues. Comparison with flow cytometric analysis. Am J Pathol. 1989;134(4):733-9.
Naresh KN, O’Conor GT, Soman CS, et al. A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin’s disease at presentation and relapse. Hum Pathol. 1997;28(5):549-55.
Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature. 1991;351(6326):453-6.
Fritsche M, Haessler C, Brandner G. Induction of nuclear accumulation of the tumor-suppression protein p53 by DNA- damaging agents. Oncogene. 1993;8(2):307-18.
Trümper LH, Brady G, Bagg A, et al. Single-cell analysis of Hodgkin and Reed-Sternberg cells: molecular heterogeneity of gene expres- sion and p53 mutations. Blood. 1993;81(11):3097-115.
Xerri L, Bouabdallah R, Camerlo J, Hassoun J. Expression of the p53 gene in Hodgkin’s disease: dissociation between im- munohistochemistry and clinicopathological data. Hum Pathol. 1994;25(5):449-54.
Chilosi M, Doglioni C, Menestrina F, et al. Abnormal expression of the p53-binding protein MDM2 in Hodgkin’s disease. Blood. 1994;84(12):4295-300.
Elenitoba-Johnson KS, Medeiros LJ, Khorsand J, King TC. P53 expression in Reed-Sternberg cells does not correlate with gene mutations in Hodgkin’s disease. Am J Clin Pathol. 1996;106(6):728-38.
Xerri L, Parc P, Bouabdallah R, Camerlo, J, Hassoun J. PCR- mismatch analysis of p53 gene mutation in Hodgkin’s disease. J Pathol. 1995;175(2):189-94.
Chen WG, Chen YY, Kamel OW, Koo CH, Weiss LM. p53 muta- tions in Hodgkin’s disease. Lab Invest. 1996;75(4):519-27.
Martinez JC, Mateo M, Sanchez-Beato M, et al. MDM2 expression in lymphoid cells and reactive and neoplastic lym- phoid tissue. Comparative study with p53 expression. J Pathol. 1995;177(1):27-34.
Weiss L, Chen YY, Liu XF, Shibata D. Epstein-Barr virus and Hodgkin’s disease. A correlative in situ hybridiza- tion and polymerase chain reaction study. Am J Pathol. 1991;139(6):1259-65.
Tzardi M, Kouvidou C, Panayiotides I, et al. Expression of p53 and mdm-2 proteins in Hodgkin’s Disease. Absence of correla- tion with the presence of Epstein-Barr virus. Anticancer Res. 1996;16(5A):2813-9.
Yuen AR, Horning SJ. Recent advances in Hodgkin’s disease. Curr Opin Hematol. 1996;3(4):273-8.
Hsu SM, Raine L, Fanger K. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29(4):577-80.
Sánchez-Beato M, Piris MA, Martínez-Montero JC, et al. MDM2 and p21WAF1/CIP1, wild-type p53-induced proteins, are regularly expressed by Sternberg-Reed cells in Hodgkin’s disease. J Pathol. 1996;180(1):58-64.
Hell K, Lorenzen J, Hansmann ML, Fellbaum C, Busch R, Fischer R. Expression of the proliferating cell nuclear antigen in the different types of Hodgkin’s disease. Am J Clin Pathol. 1993;99(5):508-603.
Schmid C, Sweeney E, Isaacson PG. Proliferating cell nuclear antigen (PCNA) expression in Hodgkin’s disease. J Pathol. 1992;168(1):1-6.
Martinez-Delgado B, Robledo M, Arranz E, et al. Correlation between mutations in p53 gene and protein expression in human lymphomas. Am J Hematol. 1997;55(1):1-8.
Niedobitek G, Rowlands DC, Young LS, et al. Overexpression of p53 in Hodgkin’s disease: lack of correlation with Epstein-Barr virus infection. J Pathol. 1993;169(2):207-12.
Smolewski P, Niewiadomska H, Blonski JZ, Robak T, Krykowski E. Expression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2 or C-erb B-2 proteins on Reed-Sternberg cells: prognostic significance in Hodgkin’s disease. Neoplasma. 1998;45(3):140-7.
Smolewski P, Niewiadomska H, Los E, Robak T. Spontaneous apoptosis of Reed-Sternberg and Hodgkin cells; clinical and pathological implications in patients with Hodgkin’s disease. Int J Oncol. 2000;17(3):603-9.
Smolewski P, Niewiadomska H, Krykowski E, Robak T. Expression of p21 and MDM-2 proteins on tumor cells in responding and non-responding patients with Hodgkin’s disease. Neoplasma. 1999;46(4):212-8.
Smoleswski P, Robak T, Krykowski E, et al. Prognostic factors in Hodgkin’s disease: multivariate analysis of 327 patients from a single institution. Clin Cancer Res. 2000;6(3):1150-60.
Brink AA, Oudejans JJ, van den Brule AJ, et al. Low p53 and high bcl-2 expression in Reed-Sternberg cells predicts poor clinical outcome for Hodgkin’s disease: involvement of apoptosis resistance? Mod Pathol. 1998;11(4):376-83.
Montalban C, Abraira V, Morente M, et al. Epstein-Barr virus- latent membrane protein 1 expression has a favorable influence in the outcome of patients with Hodgkin’s Disease treated with chemotherapy. Leuk Lymphoma. 2000;39(5-6):563-72.
Murray PG, Billingham LJ, Hassan HT, et al. Effect of Epstein- Barr virus infection on response to chemotherapy and survival in Hodgkin’s disease. Blood. 1999;94(2):442-7.
Spector N, Milito CB, Biasoli I, Luiz RR, Pulcheri W, Morais JC. The prognostic value of the expression of Bcl-2, p53 and LMP-1 in patients with Hodgkin’s lymphoma. Leuk Lymphoma. 2005;46(9):1301-6.
Montalban C, Garcia JF, Abraira V, et al. Influence of biologic markers on the outcome of Hodgkin’s lymphoma: a study by the Spanish Hodgkin’s Lymphoma Study Group. J Clin Oncol. 2004;22(9):1664-73.
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