title: 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.
abstract: Tissue inhibitors of metalloproteinases (TIMPs) are believed to possess 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 breast cancer, expression of mRNAs for TIMP-1 and TIMP-2 in the primary carcinomas from 34 breast cancer patients was related to known prognostic parameters and the clinical outcome. High levels of TIMP-1 mRNA showed 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 was 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 between these clinicopathological characteristics and the mRNA expression of the collagenolytic enzymes matrix metalloproteinase-2 and matrix metalloproteinase-9. The present data suggest that high levels of TIMP-1 and TIMP-2 mRNAs in the primary carcinomas are strongly associated with development of metastasis in breast cancer.
authors.affiliation: Departments of Tumor Biology and Pathology, The Norwegian Radium Hospital, and Hormone Laboratory, Aker Hospital, University of Oslo, Oslo, Norway. a.h.ree@dnr.uio.no
authors.forename: A H
authors.initials: AH
authors.lastname: Ree
authors.forename: V A
authors.initials: VA
authors.lastname: Florenes
authors.forename: J P
authors.initials: JP
authors.lastname: Berg
authors.forename: G M
authors.initials: GM
authors.lastname: Maelandsmo
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.forename: O
authors.initials: O
authors.lastname: Fodstad
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004790:Enzyme Induction; D004967:Estrogens; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011374:Progesterone; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D011374:Progesterone