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

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.