Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma

p27(Kipl), a cyclin-dependent kinase inhibitor, is a negative regulator of the cell cycle, and apoptosis is a genetically encoded program of cell deat h. To clarify the relationship, between the cell cycle and apoptosis, we in vestigated expression of p27, cyclin DI and apoptosis-related proteins (p53 , Bar, Bcl-2 and c-Myc) in 60 cases of oral and oropharyngeal squamous-cell carcinoma (SCC) using an immuno-histochemical approach, and evaluated spon taneous apoptosis in vivo. Our most notable finding was that spontaneous ap optosis in the p27-positive group was significantly higher than that in the p27-negative group (p = 0.028). In addition, the percentage of p27-positiv e cells was clearly correlated with that of Bar-positive cells (gamma = 0.2 88, p = 0.028) and with that of cyclin DI-positive cells (gamma = 0.416, p = 0.002). Expression of p27 was inversely associated with the clinical stag e of total tumor progression (p = 0.027). However, no correlation was found between p27 expression and the following parameters: gender, tumor size, l ymph node metastasis, overall survival and disease-free survival. Our resul ts give evidence that the action of the cell-cycle regulator p27 is closely linked with apoptosis in clinical samples from patients and indicate that over-expression of p27 might induce apoptosis in cancer cells through eleva tion of Bar expression, thereby acting on tumor progression. Int. J. Cancer (Pred. Oncol.) 84:315-320, 1999. (C) 1999 Wiley-Liss, Inc.