HIGH-LEVELS OF MESSENGER-RNAS FOR TISSUE INHIBITORS OF METALLOPROTEINASES (TIMP-1 AND TIMP-2) IN PRIMARY BREAST CARCINOMAS ARE ASSOCIATED WITH DEVELOPMENT OF DISTANT METASTASES

Tissue inhibitors of metalloproteinases (TIMPs) are believed to posses s several cellular functions, particularly the contrasting activities of inhibiting tissue-degrading enzymes and promoting cellular growth, In attempts to elucidate which of these functions may prevail in breas t cancer, expression of mRNAs for TIMP-1 and TIMP-2 in the primary car cinomas from 34 breast cancer patients was related to known prognostic parameters and the clinical outcome, High levels of TIMP-1 mRNA showe d significant correlation with the presence of lymph node metastases ( P = 0.0067), development of distant metastases (P = 0.014), and early death of the disease (P = 0.020), Elevated expression of TIMP-2 mRNA w as associated with development of distant metastases (P = 0.0055), No correlations, however, were observed between mRNA levels of TIMPs and prognostic factors such as patient age, tumor size, grade of anaplasia , or steroid receptor status; neither were any correlations found betw een these clinicopathological characteristics and the mRNA expression of the collagenolytic enzymes matrix metalloproteinase-2 and matrix me talloproteinase-9. The present data suggest that high levels of TIMP-1 and TIMP-2 mRNAs in the primary carcinomas are strongly associated wi th development of metastasis in breast cancer.