Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an inhibitor of matrix metalloproteinase (MMP) in human carcinomas. TIMP-1 is thus considered to inhibit carcinoma invasion and metastasis. On the other hand, recent reports have disclosed that TIMP-1 also possesses a growth-promoting function. The clinical significance of TIMP-1 expression has not been fully determined in breast carcinoma. We thus examined the expression of TIMP-1 mRNA in tumor tissues of 100 breast carcinoma cases by a reverse transcriptase-polymerase chain reaction assay. The expression of TIMP-1 mRNA in each case was evaluated semi-quantitatively with adjustment for the TIMP-1 expression in a control breast carcinoma cell line, MCF7. There was a significant inverse correlation between the TIMP-1 expression and lymph node metastasis (p<0.05). A multivariate analysis disclosed that TIMP-1 expression status was an independent determinant factor for lymph node metastasis. In addition, the tumors with positive estrogen or progesterone receptors showed a higher TIMP-1 mRNA expression than those without the receptors, but this did not reach statistical significance. The findings suggest that the breast tumors with high TIMP-1 expression might show less malignant potential than those with low TIMP-1 expression.

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