Lack of association between level of Plasminogen Activator Inhibitor-1 and estimates of tumor angiogenesis in early breast cancer

Abstract

Plasminogen Activator Inhibitor type-1 (PAI-1) is involved in tumor invasion and progression. High levels of PAI-1 are associated with poor prognosis in breast cancer, and PAI-1 has been shown to play a role in angiogenic processes. Since estimates of tumor angiogenesis may predict poor prognosis we studied the relationship between PAI-1 and estimates of angiogenesis in breast cancer. Tumor tissue specimens from 438 breast cancer patients were included. Median follow-up was 10.3 years. Protein levels of PAI-1 were measured using an ELISA. Angiogenesis scores were performed using a Chalkley grid. Median PAI-1 level was 0.70 ng/mg protein (range, 0 – 90 ng/mg protein) and median Chalkley count was 5.00 (range, 2.67 – 12.00). Chalkley counts were not correlated with PAI-1. In univariate analysis both increasing PAI-1 and increasing Chalkley counts evaluated as continuous parameters were significantly associated with poor disease-specific survival with RR 1.04 (95% CI 1.02 – 1.07) (p<0.0001) and RR 1.11 (95% CI 1.01 – 1.22) (p=0.04), respectively. High tertiles of PAI-1 were borderline significantly correlated with poor disease-specific survival (p=0.06), whereas high tertiles of Chalkley counts were significantly associated with poor disease-specific survival (p=0.004). Combining low/low versus high/high tertiles of Chalkley counts and PAI-1 showed actuarial 10-year survival rates of 82% versus 52% (p=0.004). High N-stage (p<0.0001), grade (p<0.0001) and increasing levels of PAI-1 (p=0.009) were independent markers of death from breast cancer. This study confirms high PAI-1 or high Chalkley counts as markers of poor prognosis in breast cancer patients, and suggests that the prognostic impact of PAI-1 is independent of its supposed involvement in tumor angiogenesis.