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

Abstract

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.

Insulin-Like Growth Factor 1 Receptor Is a Prognostic Factor in Classical Hodgkin Lymphoma

“…Increased MDM2 expression can cause downregulation of IGF-1R and in some cancers, such as soft tissue sarcoma, MDM2 expression is associated with a more malignant phenotype [40]. In cHL patients, expression of MDM2 is not associated with prognosis [41], and we did not find a correlation of MDM2 expression and absence of IGF-1R receptor expression in our patient cohort (data not shown). Another more likely explanation for this unexpected positive prognostic effect might be related to the characteristic histology of cHL with only a very small percentage of tumor cells in an abundant reactive infiltrate.…”

Clinical, Molecular, and Environmental Risk Factors for Hodgkin Lymphoma

“…Additionally, a greater proportion of Bedouin patients presented with the MC HL subtype ( P = .16), presented with advanced disease (85.7%, P = .04), and were resistant to treatment (47.4% versus 27.7%, P = .09) compared to the other groups. EBV expression was significantly more frequent, and mdm-2 (murine double minute oncogene, a negative regulator of the p53 tumor suppressor) was less frequent in the Bedouin than in any other group [29]. However, interpreting the significance of these differences is difficult given the small sample size of the study.…”