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. 2007 Mar 1;125(2):77-84.
doi: 10.1590/s1516-31802007000200003.

Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkins disease

Gevina Silva Pinheiro  1 , Maria Regina Régis Silva, Celso Arrais Rodrigues, José Kerbauy, José Salvador Rodrigues de Oliveira
Affiliations

Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkins disease

Gevina Silva Pinheiro et al. Sao Paulo Med J. .

Abstract
in English, Portuguese

Context and objective: Tumor cells in Hodgkins disease (HD) express cell proliferation markers that are evaluated according to the oncogenes involved or the expression of their proteins. Correlations between the protein expression grade and clinical data are now important for disease prognosis.

Design and setting: This was a retrospective analysis on proliferating cell nuclear antigen (PCNA), p53 and MDM2 (murine double minute-2) expression using immunohistochemistry, on formalin-fixed, paraffin-embedded tissues from diagnostic biopsies on 51 patients with HD. The study was conducted at the Division of Hematology and Transfusion Medicine, Hospital São Paulo, Universidade Federal de São Paulo.

Methods: Antigen expression was evaluated as the proportions of positive Hodgkin and Reed-Sternberg (HRS) cells and reactive lymphocytes (L), which were compared using Spearman correlation coefficients. The Friedman test was used for comparisons between the markers. The Pearson test was used to investigate associations between marker expression and clinical and laboratory parameters, marrow involvement, complete remission (CR) and overall survival (OS) rates.

Results: There was overexpression of antigen proteins in HRS, in relation to L (p < 0.001). In HRS, MDM2 was higher than p53 and PCNA (p < 0.003), while the latter two were equivalent. In L, p53 was lower than MDM2 and PCNA (p < 0.001), while the latter two were equivalent. There was no relationship between protein expression and clinical and laboratory variables or outcome.

Conclusions: PCNA, p53 and MDM2 are tumor markers for HD, but showed no clinical or prognostic significance in our analysis.

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, fixados por formol, embebidos em parafina 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 coeficiente 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 fizeram pelo coeficiente 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 significado clínico-prognóstico em nossa análise.

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Conflict of interest statement

Conflict of interest: None

Figures

Graph 1
Graph 1. Dispersion of proportional values for MDM2 expression between Hodgkin and Reed-Sternberg (HRS) cells and lymphocytes (L).
Graph 2
Graph 2. Dispersion of proportional values for p53 expression between Hodgkin and Reed-Sternberg (HRS) cells and lymphocytes (L).
Graph 3
Graph 3. Dispersion of proportional values for proliferating cell nuclear antigen (PCNA) expression between Hodgkin and Reed-Sternberg (HRS) cells and lymphocytes (L).
Figure 1
Figure 1. Photomicrograph of lymph node showing nuclear p53 expression in Reed-Sternberg cells, developed by peroxidase; 1000x magnification.
Figure 2
Figure 2. Photomicrograph of lymph node showing nuclear MDM2 expression in Hodgkin cells (upper right and left arrows) and lymphocytes (lower right arrow), developed by peroxidase; 400x magnification.
Figure 3
Figure 3. Photomicrograph showing nuclear PCNA expression in Reed-Sternberg cells and some Hodgkin cells (arrow), developed by peroxidase; 1000x magnification.
Graph 4
Graph 4. Comparison of positive lymphocyte (L) expression for MDM2, p53 and proliferating cell nuclear antigen (PCNA).
Graph 5
Graph 5. Comparison of positive Hodgkin and Reed-Sternberg (HRS) cell expression for MDM2, p53 and proliferating cell nuclear antigen (PCNA).
See this image and copyright information in PMC

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