MDM2 AND p21WAF1/CIP1, WILD-TYPE p53-INDUCED PROTEINS, ARE REGULARLY EXPRESSED BY STERNBERG-REED CELLS IN HODGKIN'S DISEASE

Sánchez‐Beato, Margarita; Piris, Miguel Á.; Martínez-Montero, Juan Carlos; Garcı́a, Juan F.; Villuendas, Raquel; García, Francisco Javier Sánchez; Orradre, J L; Martı́nez, Pedro

doi:10.1002/(sici)1096-9896(199609)180:1<58::aid-path610>3.0.co;2-w

Cited by 26 publications

(25 citation statements)

References 32 publications

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“…According to most published studies, PCNA was expressed at higher frequencies than was p53. 21,26,31 Histomorphometry was comparable to computed readings in the study by Sánchez-Beato et al 26 in 1996, for both markers. Our data show that, in the "benign" infl ammatory component of HD, there are proliferating and differentiating lymphocytes that are morphologically normal but carry positivity for proliferation markers near to HRS cells.…”

Section: Resultssupporting

confidence: 54%

“…MDM2 and p53 expression in HRS cells ranged from 30 to 80%. 12,17,21,26 In our study, concomitancy of p53 and MDM2 was found in only 37% of the cases. The lowest marker expression in reactive lymphocytes that we found, especially for p53, was comparable to previous descriptions.…”

Section: Resultscontrasting

confidence: 44%

“…The lowest marker expression in reactive lymphocytes that we found, especially for p53, was comparable to previous descriptions. 12,16,17,21,26 Positive lymphocyte reactions for PCNA and MDM2 at similar frequencies have also often been reported. [10][11][12]17,18,26,31 Our positive results for PCNA, p53 and MDM2 in HRS cells are similar to those described by Martinez-Delgado et al 29 and Sánchez-Beato et al 26 In both of those studies, double staining for p53/MDM2 was performed and variable marker expression in HRS cells was also found.…”

Section: Resultsmentioning

confidence: 75%

“…[10][11][12] In non-neoplastic small lymphocytes in HD tissues, PCNA expression is always low. [10][11][12]26,27 Schmid et al 28 evaluated 23 cases of HD by double labeling with PC-10 monoclonal antibody and CD20 (B cells), and PC-10 and CD45RO (T cells), and found positivity in 50.4% of HRS and 4.3% of lymphocytes. HRS cells express PCNA in 5 to 100% of the cases.…”

Section: Resultsmentioning

confidence: 99%

“…The application of this analysis depends on the characteristics and specifi city of the monoclonal or polyclonal antibodies for p53. 15,16,20,26,29 Latent EBV infection was initially suggested as a possible cause for p53 mutation. This hypothesis has never been confi rmed in clinical studies.…”

Section: Resultsmentioning

confidence: 99%

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Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkin’s disease

et al. 2007

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CONTEXT AND OBJECTIVE: Tumor cells in Hodgkin’s 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.

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Section: Resultssupporting

confidence: 54%

Section: Resultscontrasting

confidence: 44%

Section: Resultsmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkin’s disease

et al. 2007

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The mummified Hodgkin cell: cell death in Hodgkin's disease

1997

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This study attempts to define more clearly the morphology and ultrastructure of mummified Hodgkin cells, to determine their incidence in the different histological subtypes of Hodgkin's disease (HD), and to correlate these data with the expression of p53, bcl‐2, mdm2,and p21/WAF1. Forty‐five cases of primary HD were examined at light and electron microscopic level. DNA strand breaks were detected by the in situ end‐labelling (ISEL) and the TdT‐mediated dUTP‐digoxigenin nick end‐labelling (TUNEL) technique. Mummified Hodgkin cells display morphological features that differ from those of classical apoptosis. In contrast to apoptotic cells, mummified Hodgkin and Reed–Sternberg (HRS) cells do not react in the ISEL or TUNEL procedures and maintain the expression of antigens such as CD30 and CD15. The morphology of mummified tissue cells could be simulated by CD95‐mediated induction of apoptosis in the Hodgkin cell line HDLM2 if internucleosomal DNA fragmentation was inhibited by zinc ions. The highest incidence of mummified cells was found in the nodular sclerosis and mixed cellularity subtypes, whereas the lowest frequency was observed in nodular paragranuloma. The frequency was independent of p53, bcl‐2, p21,and mdm2 expression. p21 and mdm2 immunoreactivity of HRS cells was correlated with p53 status. HRS cells in nodular paragranuloma were virtually negative for p21/WAF1 or bcl‐2. Classical apoptotic cells reacting in the TUNEL and ISEL procedures are found in all subtypes of HD and are derived from the non‐neoplastic cellular background. In conclusion, mummified Hodgkin cells display features of apoptosis lacking the internucleosomal DNA fragmentation. The pattern of the p53‐transactivated genes mdm2 and p21/WAF1 suggests that inactivating mutations of p53 are rare in HD. © 1997 John Wiley & Sons, Ltd.

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Apoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1

et al. 2000

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MDM2 AND p21WAF1/CIP1, WILD-TYPE p53-INDUCED PROTEINS, ARE REGULARLY EXPRESSED BY STERNBERG-REED CELLS IN HODGKIN'S DISEASE

Cited by 26 publications

References 32 publications

Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkin’s disease

Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkin’s disease

The mummified Hodgkin cell: cell death in Hodgkin's disease

Apoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1

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