Clinical relevance of amphiregulin and VEGF in primary breast cancers.

ABSTRACT

The characterization of novel prognostic markers in breast cancer is necessary to improve the identification of high-risk populations. In our study, the prognostic significance of VEGF and amphiregulin (AR) was investigated and compared to conventional prognostic factors in primary breast cancers. The analysis was performed using enzyme-linked immuno-assay in a series of 193 patients, and univariate and multivariate analysis were performed in the overall population as well as in pre- and post-menopausal patients subdivided in node-negative (N-) and node-positive (N+) subsets. AR (median, 44.8 pg/mg protein) appeared strongly correlated with progesterone receptors (PgR) (p = 0.0018) in the premenopausal N+ population, and with uPA (p= 0.020) and VEGF (p= 0.0053) in the postmenopausal/N+ patients. Despite these attractive data, AR expression was not significant for recurrence or survival outcome. Data revealed strong correlation between VEGF and uPA, and PAI-1, in the N+ population. Moreover, patients with high VEGF levels displayed poor outcome, with an increased risk for N+ subset. These data were confirmed by multivariate analysis that presented histologic grade (HR, 10.55, p = 0.001) and VEGF (HR, 3.89, p = 0.03) as the prominent prognostic markers for overall survival for the N+ population. Furthermore, infiltrating ductal carcinomas (IDC) were shown to express higher levels of both uPA (p < 0.0001) and VEGF (p = 0.002) than intralobular carcinomas. This retrospective study reinforces the pejorative biological role of VEGF in the progression of breast tumors. Our data also suggest that VEGF and uPA might play particular role in the biology and progression of IDC.