Overexpression of phosphorylated p27 Kip1 at threonine 187 may predict outcome in aggressive B-cell lymphomas

Leuk Lymphoma. 2011 May;52(5):814-22. doi: 10.3109/10428194.2011.555026. Epub 2011 Feb 21.

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.

MeSH terms

  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymphoma, B-Cell / mortality
  • Lymphoma, B-Cell / pathology*
  • Phosphorylation
  • Predictive Value of Tests*
  • Prognosis
  • Survival Analysis
  • Threonine / metabolism*

Substances

  • Cyclin-Dependent Kinase Inhibitor p27
  • Threonine