Elevated levels of MDM-2 and p53 expression are associated with high grade non-Hodgkin's lymphomas

The role of p53 in the evolution of non-Hodgkin's lymphomas (NHL) is unclear. Mutations of the p53 gene appear to be relatively uncommon but stabilized p53 protein, as detected by immunohistochemistry, has indicated a more frequent involvement of p53. As dysfunction of p53 protein has also been suggested to occur after overexpression of the mdm-2 protein, we have therefore investigated a series of non-malignant hyperplastic reactive lymphoid tissues and NHL to examine whether the levels of expression of MDM-2 correlated to positivity of p53 protein staining. Northern blot analysis of MDM-2 expression was compared to glucose-6-phosphate dehydrogenase (G6PD) expression by densitometry to quantify the relative levels of MDM-2 expression. Consistent low levels of MDM-2 expression were observed in non-malignant lymphoid tissue and in low grade NHL, however, 13/15 high grade NHL exhibited a 2-15-fold increase in MDM-2 expression. Interestingly similar elevations in p53 mRNA expression were also observed in 6/15 high grade NHL. Positive staining of the p53 protein did not, however, correlate with elevated mRNA levels of either MDM-2 or p53. The significance of these observations is discussed.