Abstract
e22208 Background: In a normal mammary gland D-type and E1 cyclins play a significant role in the cell cycle control. Not surprisingly, they are considered to have an oncogenic potential and belong among the most commonly overexpressed genes in breast cancer. Besides, cyclin D2 overexpression is associated with an inhibition of cyclin D1 phosphorylation and with an increase of the p27 inhibitor. Such a complex cell cycle regulation is realized at the quantitative level and results in the proliferation activity control. Therefore, we analyzed the molecules involved in the cell cycle regulation together with the proliferation marker Ki-67 at the quantitative level. Methods: We examined cyclin D1, D2, D3, E1, and p27 and Ki-67 mRNA level by qRT-PCR in 95 fresh frozen invasive ductal breast carcinomas and in 15 non-neoplastic breast tissues. In patients with the carcinoma we correlated the mRNA levels with the ERBB-2 positivity, estrogen and progesterone receptor status, proliferation rate, cyclin D1 protein expression, CCDN1 gene amplification, grade, lymph node status, tumor size and age at diagnosis. We looked for a correlation with overall survival and time to event in 70 patients with available long term follow-up data. Results: The only significant association found in this analysis related to cyclin D2. In comparison with non-neoplastic controls we observed cyclin D2 mRNA down-regulation in breast carcinomas and it was inversely correlated with a higher tumor grade and its greater size, which are considered as parameters related to a less favorable prognosis. Moreover, cyclin D2 mRNA down-regulation together with cyclin D1 and D3 up-regulation revealed a significant association with decreased overall survival and time to event in multivariate analysis. Conclusions: The data indicate that down-regulated cyclin D2 mRNA correlates with a greater malignant potential of breast carcinoma. Thus, establishing cyclin D2 mRNA level may be used as a prognostically relevant investigation and along with other prognostically related data it has a potential in helping to identify patients with an adverse prognosis. Support CZ.2.16/3.1.00/24022 and 00064203.
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