Non-Small Cell Lung Cancer Prognostic Role of the Cyclin-dependent Kinase Inhibitor p27 in

Despite its potential role as a tumor suppressor, p27 gene, a member of the Cip/Kip family of cydin-dependent kinase inhibitor genes, has never been found mutated in human tumors. We investigated p27 protein ex pression in a series of 108 non-small cell lung cancers (57.4% stage 1, 16.7% stage 2, and 25.9% stage 3) to determine whether the lack or altered expression of this protein correlates with neoplastic transforma don and/or progression. We performed immunohistochemistry and West em blotanalysisof eachspecimen.Wefoundthat tumorsexpressinglow to undetectable levels of p27 contained high p27 degradation activity. When we evaluated the outcome of the patients in relationship to p27 expression, we found p27 to be a prognostic factor correlating with the overall survival times (P = 0.0012). The possibility of a simple assay, such as the immunohistochemical analysis ofp27 expression on routinely formalin-fixed, paraffin-embedded specimens, has considerable value for the prognosis of patients who Un dergo surgical resection. In addition, confirmation of the involvement of the proteasome-mediated proteolysis in p27 degradation should stimulate new strategies of nonsurgical treatments of non-small cell lung cancer.