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Enhanced mRNA expression of tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in breast carcinomas is correlated with adverse prognosis

Tissue inhibitor of metalloproteinase‐1 (TIMP‐1) has emerged as a multifunctional protein with the contrasting activities of inhibiting tissue‐degrading enzymes and promoting cellular growth. In an attempt to elucidate the clinical significance of TIMP‐1 in breast cancer, the expression of TIMP‐1 mRNA was evaluated in 117 invasive breast carcinomas by mRNA in situ hybridization, in correlation with clinicopathological parameters, immunohistochemical prognostic factors (Ki‐67, c‐erb‐B‐2, bcl‐2) and clinical outcome. TIMP‐1 was detected in stromal cells in areas within the tumours and at the tumour margin. High TIMP‐1 mRNA expression in the marginal portion of the tumours was significantly correlated with lymph node metastasis (p<0.05) and c‐erbB‐2 expression (p<0.05). On the other hand, increased TIMP‐1 mRNA expression within the tumours showed a statistically significant correlation with ER detection (p<0.01). Multivariate analysis revealed worse survival for patients with high TIMP‐1 mRNA expression in the marginal portion of the tumours; the subgroup of these patients co‐expressing high levels of TIMP‐1 mRNA within the tumours as well had even worse survival (p=0.042). In conclusion, our data support the multifunctional role of TIMP‐1, particularly its growth‐promoting activity, on the basis of its significant correlation with lymph node metastasis and adverse prognosis. In addition to the latter property, a probable association of TIMP‐1 with tumour cell differentiation is suggested by its topographical correlation with ER detection. Copyright © 2002 John Wiley & Sons, Ltd.