p27(KIP1) is abnormally expressed in diffuse large B-cell lymphomas and isassociated with an adverse clinical outcome

Cell cycle progression is regulated by the combined action of cyclins, cycl in-dependent kinases (CDKs), and CDK-inhibitors (CDKi), which are negative cell cycle regulators. p27(KIP1) is a CDKi key in cell cycle regulation, wh ose degradation is required for G1/S transition. In spite of the absence of p27(KIP1) expression in proliferating lymphocytes, some aggressive B-cell lymphomas have been reported to show an anomalous p27(KIP1) staining. We an alysed p27(KIP1) expression in a series of Diffuse Large B-cell Lymphoma (D LBCL), correlating it with the proliferative index and clinical outcome, to characterize the implications of this anomalous staining in lymphomagenesi s in greater depth. For the above mentioned purposes, an immunohistochemica l technique in paraffin-embedded tissues was employed, using commercially a vailable antibodies, in a series of 133 patients with known clinical outcom es. Statistical analysis was performed in order to ascertain which clinical and molecular variables may influence outcome, in terms of disease-free su rvival (DFS) and overall survival (OS). The relationships between p27(KIP1) and MIB-1 (Ki-67) were also tested. An abnormally high expression of p27(K IP1) was found in lymphomas of this type. The overall correlation between p 27(KIP1) and MIB-1 showed there to be no significant relationship between t hese two parameters, this differing from observations in reactive lymphoid and other tissues. Analysis of the clinical relevance of these findings sho wed that a high level of p27(KIP1) expression in this type of tumour is an adverse prognostic marker, in both univariate and multivariate analysis. Th ese results show that there is abnormal p27(KIP1) expression in DLBCL, with adverse clinical significance, suggesting that this anomalous p27(KIP1) pr otein may be rendered non-functional through interaction with other cell cy cle regulator proteins.