Overexpression of cyclinD1 predicts for poor prognosis in estrogen receptor‐negative breast cancer patients

Abstract

CyclinD1 plays a critical role in regulating cell cycle progression. CyclinD1 mRNA and protein are overexpressed in approximately 50% of primary breast cancer cases. However, its clinical significance as a predictive factor remains unclear. One hundred and seventy-three female patients diagnosed with invasive ductal carcinoma who had undergone a mastectomy (161 patients) or breast-conserving surgery (12 patients) were followed up for 6 -119 months (median 86 months) postoperatively. Immunoreactivity for monoclonal anti-cyclinD1 antibody (clone DCS-6) with paraffin-embedded carcinoma tissues was investigated using a labeled streptavidin-biotin method. Overexpression of cyclinD1 was found in 42% (73 of 173), and strongly correlated with estrogen receptor (ER) expression (p < 0.000001). Univariate analysis revealed no association between overexpression of cyclinD1 and overall survival or relapse-free survival in all patient groups. However, in the ER-negative subgroup (n ‫؍‬ 75), overexpression of cyclinD1 was significantly correlated with shorter overall survival (p ‫؍‬ 0.018) and relapse-free survival (p ‫؍‬ 0.014) as well as the lymph node status and tumor size. In contrast, there were no significant associations between overexpression of cyclinD1 and clinical outcome in the ER-positive subgroup. According to Cox's multivariate analysis in the ER-negative subgroup, overexpression of cyclinD1 had the most significant effect on overall survival (p ‫؍‬ 0.02) and relapse-free survival (p ‫؍‬ 0.0058), followed by nodal status and histologic grade. These findings suggest that overexpression of cyclinD1 is an independent prognostic indicator in ER-negative breast cancer patients.

Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

“…35 In addition, in our previous study, cyclin D1 ablation in human oral squamous cell carcinoma cells was associated with increased cisplatin chemosensitivity. 22 Although it has been reported that high EZH2 expression is correlated with the up-regulation of cyclin D1 in gastric cancer, pharmacologic inhibition of EZH2 leads to the down-regulation of cyclin D1 levels in skin cancer.…”

Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer

“…High cyclin D1 expression has been associated with less aggressive tumour characteristics including hormone receptor positivity. It has associated with low tumour grade [4,6,7,14], although a few studies have failed to confirm this [3,5,11]. The role of cyclin D1 in breast cancer prognosis remains unclear; some studies show correlation to poor, some to good prognosis, and some have not been able to show any correlation.…”

“…High cyclin D1 expression is associated with non-aggressive features in breast cancer including estrogen receptor (ER) positivity [3][4][5][6][7][8]. Estrogen stimulates cyclin D1 expression and cyclin D1 is an important mediator of estrogen stimulation of cell cycle progression [9].…”

Expression of Cyclin D1 and its relationship to hormone receptors and survival in breast cancer

“…[8][9][10] There are reports that cyclins may play a role in some of the hormone sensitive breast cancer cases that are resistant to tamoxifen and the mechanism of action of tamoxifen is affected by the deterioration of control of cell cycle. [11,12] However there is no consensus in the literature on the role of Cyclin D1 in breast cancer biology and its prognostic and predictive value.…”