Over-expression of cyclin A is highly associated with early relapse and reduced survival in patients with primary breast carcinomas

Progression through the mammalian cell cycle is facilitated by cyclin-cycli n-dependent kinase (cdk) complexes, which are activated at specific points during the cell cycle. Alteration in cyclin-cdk complexes may lead to alter ed cell cycle and tumorigenesis. In this study, we analyzed expression of c yclins A, D1, D3 and E in tumor tissue from 170 patients with primary invas ive breast carcinomas. Immunohistochemical methods were used to detect prot ein expression of these cyclins. We detected positive immunoreactivity in 5 5 (32%), 22 (13%), 38 (22%) and 37 (21.8%) of the samples for cyclins A, D1 , D3 and E, respectively. A highly statistically significant association wa s observed between expression of cyclin A and early relapse (p = 0.001 univ ariate analysis, p = 0.006 multivariate analysis) as well as cancer-specifi c death (p < 0.0001) during the follow-up time. No association was observed between cyclin D1 or cyclin E, respectively, and relapse of disease or sur vival, while cyclin D3 over-expression was associated with development of m etastases during follow-up (p = 0.005 univariate analysis, p = 0.01 multiva riate analysis). However, cyclin D3 did not show any statistically signific ant association when cancer-specific death was examined in a multivariate a nalysis (Cox regression for survival function). (C) 2001 Wiley-Liss, Inc.