Overexpression of
tissue inhibitor of metalloproteinase-1 at either the
messenger RNA or
protein level has been related to a poorer prognosis in
breast cancer. We investigated the role of
tissue inhibitor of metalloproteinase-1 tissue expression, which was evaluated by immunohistochemistry staining of
paraffin-embedded samples, as a possible prognostic
indicator in
breast cancer. The study included 266 patients treated by primary surgery.
Tumors were scored
tissue inhibitor of metalloproteinase-1 positive when at least 10% of the cells showed moderate or strong staining. Staining was observed in 76 (28.6%) patients; by multivariate analysis, factors independently associated with
tissue inhibitor of metalloproteinase-1 positivity included more than 9 metastatic axillary nodes, high Mib-1 expression, and positivity for
plasminogen activator inhibitor and CD44. With a median follow-up of 125 months,
tissue inhibitor of metalloproteinase-1 expression showed a significant prognostic role in disease-free and overall survival by univariate analysis. Multivariate analysis confirmed an independent negative prognostic impact of
tissue inhibitor of metalloproteinase-1 on overall but not disease-free together with high values of Mib-1. The number of involved axillary nodes, and triple negativity were independent predictors of either poorer disease-free or overall survival. In our study,
tissue inhibitor of metalloproteinase-1 expression was significantly related to markers of
tumor aggressiveness and was a powerful
indicator of poorer prognosis, with a difference in 10-year disease-free and overall survival of 14% and 28%, respectively, between tissue inhibitor of metalloproteinase-1-negative and tissue inhibitor of metalloproteinase-1-positive cases. Expression of
tissue inhibitor of metalloproteinase-1 also was an independent prognostic factor in node-positive cases, indicating a possible role of
tissue inhibitor of metalloproteinase-1 as a marker of reduced chemosensitivity. Thus,
tissue inhibitor of metalloproteinase-1 may have a role in clinical practice as a prognostic and predictive factor and a possible target for future
therapies.