title: Overexpression of phosphorylated p27 Kip1 at threonine 187 may predict outcome in aggressive B-cell lymphomas.
abstract: Phosphorylation of p27(Kip1) at threonine 187 (pThr187-p27(Kip1)) occurs frequently in the development of human tumors, directing protein polyubiquitination and subsequent proteasomal degradation. We investigated the immunoexpression of p27(Kip1) and pThr187-p27(Kip1) in 126 B-cell lymphomas and their relation to proliferative activity and clinical parameters. Increased levels of p27(Kip1) and pThr187-p27(Kip1) were significantly correlated with indolent and aggressive lymphomas, respectively (p < 0.001). pThr187-p27(Kip1) expression showed a strong positive correlation with proliferation index in aggressive (p = 0.01) and indolent (p < 0.001) subgroups. Survival analysis revealed that pThr187-p27(Kip1) was an unfavorable prognostic factor for disease-free (p = 0.019) and overall survival (p = 0.003) in aggressive lymphomas. Cox regression analysis demonstrated that the prognostic value of pThr187-p27(Kip1) was independent of the international prognostic index (IPI) score, tumor stage, patient age, and serum lactate dehydrogenase (LDH) level. Overall, our results suggest that high levels of pThr187-p27(Kip1) may predict a worse clinical outcome in patients with aggressive lymphomas.
authors.affiliation: Department of Pathology, Division of Hematology, University of Patras Medical School, Patras, Greece.
authors.forename: Chaido
authors.initials: C
authors.lastname: Sirinian
authors.forename: Argiris
authors.initials: A
authors.lastname: Symeonidis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Giannakoulas
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Zolota
authors.forename: Maria
authors.initials: M
authors.lastname: Melachrinou
mesh_terms: D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000401:mortality / Q000473:pathology*; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D013912:Threonine / Q000378:metabolism*
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D013912:Threonine