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 cyclinD l 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 cyclinD 1 is an independent prognostic indicator in ER-negative breast cancer patients. © 2002 Wiley-Liss, Inc.