p27(KIP1) is abnormally expressed in Diffuse Large B-Cell Lymphomas and is associated with an adverse clinical outcome

Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors (CDKi), which are negative cell cycle regulators. p27(KIP1) is a CDKi key in cell cycle regulation, whose 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 analysed p27(KIP1) expression in a series of Diffuse Large B-cell Lymphoma (DLBCL), correlating it with the proliferative index and clinical outcome, to characterize the implications of this anomalous staining in lymphomagenesis in greater depth. For the above mentioned purposes, an immunohistochemical technique in paraffin-embedded tissues was employed, using commercially available antibodies, in a series of 133 patients with known clinical outcomes. Statistical analysis was performed in order to ascertain which clinical and molecular variables may influence outcome, in terms of disease-free survival (DFS) and overall survival (OS). The relationships between p27(KIP1) and MIB-1 (Ki-67) were also tested. An abnormally high expression of p27(KIP1) was found in lymphomas of this type. The overall correlation between p27(KIP1) and MIB-1 showed there to be no significant relationship between these two parameters, this differing from observations in reactive lymphoid and other tissues. Analysis of the clinical relevance of these findings showed that a high level of p27(KIP1) expression in this type of tumour is an adverse prognostic marker, in both univariate and multivariate analysis. These results show that there is abnormal p27(KIP1) expression in DLBCL, with adverse clinical significance, suggesting that this anomalous p27(KIP1) protein may be rendered non-functional through interaction with other cell cycle regulator proteins. © 1999 Cancer Research Campaign