Cyclin D1 expression in non-small-cell lung cancers: its association with altered p53 expression, cell proliferation and clinical outcome

Cyclin D1, like p16(INK4) (p16) and retinoblastoma (RB) proteins, participa tes in the cell cycle control at the GI-S transition. We have previously de monstrated altered p16 and RE protein status in non-small-cell lung cancers (NSCLCs) and their potential synergistic effect with altered p53 protein o n proliferative activity (Kinoshita et al (1996) Cancer Res 56. 5557-5562). In the present study, cyclin D1 expression was studied by immunohistochemi stry in the same cohort of 111 resected NSCLCs as in our previous study, an d the amount of the cyclin D1 gene was analysed by Southern blot analysis i n 29 NSCLCs. Cyclin D1 expression was analysed in relation to the status of p53, p16 and RE proteins, and proliferative activity determined by the Ki- 67 index. It was also analysed in relation to survival of 77 patients with NSCLCs which were potentially curatively resected between 1990 and 1995. We found that: (1) cyclin D1 was expressed in 13 (11.7%) of 111 NSCLCs; (2) t he cyclin D1 gene was neither significantly amplified nor rearranged; (3) c yclin D1 expression significantly correlated with altered p53 protein expre ssion (P = 0.04), whereas it did not correlate with p16 and RE protein stat us, (4) proliferative activity tended to be higher in cyclin D1-positive () tumours than in cyclin D1-negative (-) tumours, although this difference was not statistically significant (P = 0.08); and (5) patients with cyclin D1+ tumours survived longer than patients with cyclin D1- tumours (5-year s urvival rates, 89% and 64% respectively, by the Kaplan-Meier method; P = 0. 045 by the log-rank test), and cyclin D1 expression tended to be a favourab le prognostic factor (P = 0.08 in univariate analysis). These findings sugg est the involvement of cyclin D1 in the development and progression of NSCL Cs, their proliferative activity and clinical outcome of NSCLC patients.