Stromelysin-3 Protein Expression in Invasive Breast Cancer: Relation to Proliferation, Cell Survival and Patients’ Outcome

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Abstract
Matrix metalloproteinases constitute one of the major extracellular matrix degrading enzymic families implicated in cancer development. Stromelysin-3 in particular, a member of the matrix metalloproteinases belonging to the stromelysins’ subgroup, seems to be closely related to invasiveness and tumor progression. In this study, we proceeded to the evaluation of stromelysin-3 protein’s expression in paraffin sections of 133 cases of invasive breast carcinomas and statistically estimated its relations with known clinicopathological prognostic parameters and patients’ survival, proliferation markers Ki-67 and TopoIIα and the antiapoptotic protein bcl-2. Presence of stromelysin-3 was immunodetected, in the 73% of our cases, in stromal cells (65%) and in epithelial tumor cells (26.26%). Stromelysin-3 epithelial positivity presented statistically significant correlations with TopoIIα and Ki-67 proliferation indices (P = .042 and P = .031, respectively) and worse disease outcome through multivariate statistics (P = .014). Stromelysin-3 fibroblastic expression was significantly associated with nuclear grade (P = .024), ductal histological type (P = .037), TopoIIα (P = .001) and Ki-67 (P = .019), inversely with bcl-2 protein (P = .027) and with adverse overall survival through univariate analysis (P = .017). The subgroup of patients with stromelysin-3 co-expression in stromal and malignant epithelial cells showed statistically significant associations with Ki-67 and TopoIIα (P = .019, P < .0001, respectively), an inverse one with bcl-2 protein (P = .027) and furthermore with impaired survival (P = .002) through multivariate analysis. In conclusion, stromelysin-3 protein expression correlated with proliferation indices TopoIIα and Ki-67 and the anti-apoptotic protein bcl-2, data confirming stromelysin-3’s contribution to breast cancer progression. Moreover its expression was shown to have a direct negative effect on patients’ survival, especially in the subgroup of patients with simultaneous epithelial and stromal expression.

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