title: 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.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus C, Denmark. bvo@oncology.dk
authors.forename: Birgitte Vrou
authors.initials: BV
authors.lastname: Offersen
authors.forename: Rikke
authors.initials: R
authors.lastname: Riisbro
authors.forename: Ann
authors.initials: A
authors.lastname: Knoop
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000401:mortality / Q000503:physiopathology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010865:Pilot Projects; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011379:Prognosis; D011446:Prospective Studies; D013534:Survival; D015996:Survival Rate; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1