EXPRESSION OF CYCLIN-E AND THE CYCLIN-DEPENDENT KINASE INHIBITOR P27 IN MALIGNANT-LYMPHOMAS - PROGNOSTIC IMPLICATIONS

Cyclin E and the cyclin-dependent kinase inhibitor p27 are two importa nt regulators of the G1-S transition modulating the activity of cyclin -dependent kinases. Aberrations in the cell cycle control are often ob served in tumors and might even be mandatory in tumor development. To investigate the importance of cell-cycle defects in malignant lymphoma s we have characterized the expression of cyclin E and p27 in 105 newl y diagnosed lymphomas using immunohistochemistry. A significant, inver se correlation between p27 and cyclin E expression was observed (r(s) = -.24, P =.02) and both proteins correlated with the S-phase fraction (r(s) = -.35, P < .001 and r(s) = .45, P < .001, respectively). The i nverse relationship between p27 expression and proliferation was abrog ated in some lymphomas, suggesting that p27 down-regulation can repres ent a genuine aberration. Survival analysis was performed in 105 patie nts with a median observation time of 86 months. Low p27 and high cycl in E expression were significantly associated with a poor prognosis (P = .0001 and .03, respectively). In a multivariate Cox analysis, p27 e xpression, stage, serum lactate dehydrogenase level, grade, and age we re independent prognostic factors, in contrast to S-phase fraction and cyclin E expression. This is the first report showing that p27 expres sion in malignant lymphomas has independent prognostic significance, w hich necessitates future studies regarding its more precise biological role in lymphoid tumorogenesis. (C) 1998 by The American Society of H ematology.