HER-2/neu and fibrinolytic factors in human breast cancer

HER-2/neu status and t-PA, u-PA, and PAI-1 cytosol content were evaluated in 88 primary breast cancer patients to determine the relationships between these parameters. HER-2/neu was amplified in 24% (20/84) of tumor samples and overexpressed in 28% (14/50). In the overall series, median t-PA, u-PA and PAT-1 contents, measured by the enzyme-linked immunoassay (ELISA), resulted in 1.7, 1.1 and 1.0 ng/mg cytosol protein (cyt prot), respectively. HER-2/neu overexpressed cases showed higher u-PA levels than those normally expressed whereas t-PA and PAI-1 levels did not vary in HER-2/neu altered and non altered cases. The t-PA levels did not differ in cases with or without HER-2/neu alterations, when separately considering the node-negative and node-positive cases. A significant relationship between t-PA levels and HER-2/neu alterations was observed only in the ER⁺ tumors: t-PA levels were lower in amplified and overexpressed cases (1.4 versus 2.5 ng/mg cyt prot in amplified and single copy gene, respectively; 1.6 versus 2.3 ng/mg cyt prot in overexpressed and normally expressed cases, respectively). Therefore, t-PA and HER-2/neu could provide additional prognostic information for ER-negative patients.