PROGNOSTIC ROLE OF THE CYCLIN-DEPENDENT KINASE INHIBITOR P27 IN NONSMALL CELL LUNG-CANCER

Despite its potential role as a tumor suppressor, p27 gene, a member o f the Cip/Kip family of cyclin-dependent kinase inhibitor genes, has n ever been found mutated in human tumors. We investigated p27 protein e xpression 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 transfor mation and/or progression. We performed immunohistochemistry and Weste rn blot analysis of each specimen. We found that tumors expressing low 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 t he overall survival times (P = 0.0012). The possibility of a simple as say, such as the immunohistochemical analysis of p27 expression on rou tinely formalin-fixed, paraffin-embedded specimens, has considerable v alue for the prognosis of patients who undergo surgical resection. In addition, confirmation of the involvement of the proteasome-mediated p roteolysis in p27 degradation should stimulate new strategies of nonsu rgical treatments of non-small cell lung cancer.