Expression of Cyclin E and the Cyclin-Dependent Kinase Inhibitor p27 in Malignant Lymphomas—Prognostic Implications

Open Access
Publisher Website
Google Scholar
Abstract
Cyclin E and the cyclin-dependent kinase inhibitor p27 are two important regulators of the G1-S transition modulating the activity of cyclin-dependent kinases. Aberrations in the cell cycle control are often observed in tumors and might even be mandatory in tumor development. To investigate the importance of cell-cycle defects in malignant lymphomas we have characterized the expression of cyclin E and p27 in 105 newly diagnosed lymphomas using immunohistochemistry. A significant, inverse correlation between p27 and cyclin E expression was observed (rs = −.24, P = .02) and both proteins correlated with the S-phase fraction (rs = −.35, P < .001 andrs = .45, P < .001, respectively). The inverse relationship between p27 expression and proliferation was abrogated in some lymphomas, suggesting that p27 downregulation can represent a genuine aberration. Survival analysis was performed in 105 patients with a median observation time of 86 months. Low p27 and high cyclin E expression were significantly associated with a poor prognosis (P = .0001 and .03, respectively). In a multivariate Cox analysis, p27 expression, stage, serum lactate dehydrogenase level, grade, and age were independent prognostic factors, in contrast to S-phase fraction and cyclin E expression. This is the first report showing that p27 expression in malignant lymphomas has independent prognostic significance, which necessitates future studies regarding its more precise biological role in lymphoid tumorogenesis. © 1998 by The American Society of Hematology.