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

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Abstract
Progression through the mammalian cell cycle is facilitated by cyclin–cyclin-dependent kinase (cdk) complexes, which are activated at specific points during the cell cycle. Alteration in cyclin–cdk complexess may lead to altered cell cycle and tumorigenesis. In this study, we analyzed expression of cyclins A, D1, D3 and E in tumor tissue from 170 patients with primary invasive breast carcinomas. Immunohistochemical methods were used to detect protein expression of these cyclins. We detected positive immunoreactivity in 55 (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 was observed between expression of cyclin A and early relapse (p = 0.001 univariate analysis, p = 0.006 multivariate analysis) as well as cancer-specific 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 survival, while cyclin D3 over-expression was associated with development of metastases during follow-up (p = 0.005 univariate analysis, p = 0.01 multivariate analysis). However, cyclin D3 did not show any statistically significant association when cancer-specific death was examined in a multivariate analysis (Cox regression for survival function).