title: p27KIP1 is abnormally expressed in Diffuse Large B-cell Lymphomas and is associated with an adverse clinical outcome.
abstract: 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. p27KIP1 is a CDKi key in cell cycle regulation, whose degradation is required for G1/S transition. In spite of the absence of p27KIP1 expression in proliferating lymphocytes, some aggressive B-cell lymphomas have been reported to show an anomalous p27KIP1 staining. We analysed p27KIP1 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 p27KIP1 and MIB-1 (Ki-67) were also tested. An abnormally high expression of p27KIP1 was found in lymphomas of this type. The overall correlation between p27KIP1 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 p27KIP1 expression in this type of tumour is an adverse prognostic marker, in both univariate and multivariate analysis. These results show that there is abnormal p27KIP1 expression in DLBCL, with adverse clinical significance, suggesting that this anomalous p27KIP1 protein may be rendered non-functional through interaction with other cell cycle regulator proteins.
authors.affiliation: Department of Pathology, Virgen de la Salud Hospital, Toledo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sáez
authors.forename: E
authors.initials: E
authors.lastname: Sánchez
authors.forename: M
authors.initials: M
authors.lastname: Sánchez-Beato
authors.forename: M A
authors.initials: MA
authors.lastname: Cruz
authors.forename: I
authors.initials: I
authors.lastname: Chacón
authors.forename: E
authors.initials: E
authors.lastname: Muñoz
authors.forename: F I
authors.initials: FI
authors.lastname: Camacho
authors.forename: J C
authors.initials: JC
authors.lastname: Martínez-Montero
authors.forename: M
authors.initials: M
authors.lastname: Mollejo
authors.forename: J F
authors.initials: JF
authors.lastname: García
authors.forename: M A
authors.initials: MA
authors.lastname: Piris
mesh_terms: D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D015996:Survival Rate; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D016213:Cyclins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27