Expression of p27(kip) and other cell cycle regulators in malignant peripheral nerve sheath tumors and neurofibromas: the emerging role of p27(kip) in malignant transformation of neurofibromas.

There is little information regarding the status of cell cycle regulators in malignant peripheral nerve sheath tumors (MPNSTs) and neurofibromas (NFs). In this study, we investigated patterns of expression of p53 and pRB, cyclin-dependent kinase inhibitors (CKIs) p21 and p27, as well as cyclins D1 and E, in a cohort of 35 well-characterized MPNSTs and 16 NFs. These phenotypes were correlated with proliferative index, as assessed by Ki-67, as well as clinicopathological parameters of poor outcome. p53 nuclear overexpression was found in 10 of 35 (29%) MPNSTs, and it was lacking in NFs (P = 0.02). There were no differences in the patterns of expression of pRB, cyclin D1, and p21 between MPNSTs and NFs. However, p27 nuclear expression was present in most NFs, but it was absent in the majority of MPNSTs, which displayed cytoplasmic staining (P < 0.001). Nuclear cyclin E expression was more pronounced in MPNSTs than in NFs. We observed inverse patterns of expression for nuclear p27 and nuclear cyclin E expression. The staining profiles of cytoplasmic p27 and nuclear cyclin E expression were found to be statistically associated (P = 0.01). High Ki-67 expression was found in 20 of 34 (59%) MPNSTs but was absent in NFs (P < 0.001). Furthermore, detection of cytoplasmic p27 expression was found to be a prognostic factor for poor survival in MPNSTs (P = 0.03, relative risk = 2.4).