Clinical significance of cyclin-dependent kinase inhibitor p27(Kip1) expression and proliferation in non-Hodgkin's lymphoma: independent prognostic value of p27(Kip1)

The cyclin-dependent kinase inhibitor p27(Kip1) is a negative cell cycle re gulator linking extracellular growth-regulatory signals to the cell cycle m achinery in G(1). We investigated the pattern and prognostic value of p27(K ip1) expression in a population-based group of 203 non-Hodgkin's lymphoma ( NHL) patients. The expression of p27(Kip1) was identified by immunohistoche mistry and correlated with Ki-67 expression and clinical features. Correlat ion with outcome was determined using uni- and multivariate analysis strati fied by clinical grade. Except for very aggressive NHL, there was a negativ e correlation between p27(Kip1) and Ki-67 expression. Low expression of p27 (Kip1), defined as nuclear p27(Kip1) expression in <40% of malignant cells, was predictive of poor survival in indolent and aggressive NHL. However, e ven in this regard, very aggressive lymphomas behaved differently as those with low p27(Kip1) expression tended to do better. Likewise, a high prolife ration rate (Ki-67 >40%) was associated with poor survival in indolent and aggressive lymphomas. Multivariate analysis using the proportional hazards model showed that only p27(Kip1), and not Ki-67, maintained independent pro gnostic significance in indolent and aggressive lymphomas (relative risk = 2.0; P = 0.0095). The low cost and simplicity of this standard immunohistoc hemistry analysis makes p27(Kip1) a promising and suitable prognostic marke r in routine diagnostic laboratories in a standard diagnostic panel.