{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:42:01Z","timestamp":1791121321274,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,4,23]],"date-time":"2002-04-23T00:00:00Z","timestamp":1019520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Greek Ministry of Development"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tissue inhibitor of metalloproteinase\u20101 (TIMP\u20101) has emerged as a multifunctional protein with the contrasting activities of inhibiting tissue\u2010degrading enzymes and promoting cellular growth. In an attempt to elucidate the clinical significance of TIMP\u20101 in breast cancer, the expression of TIMP\u20101 mRNA was evaluated in 117 invasive breast carcinomas by mRNA\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization, in correlation with clinicopathological parameters, immunohistochemical prognostic factors (Ki\u201067, c\u2010erb\u2010B\u20102, bcl\u20102) and clinical outcome. TIMP\u20101 was detected in stromal cells in areas within the tumours and at the tumour margin. High TIMP\u20101 mRNA expression in the marginal portion of the tumours was significantly correlated with lymph node metastasis (\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.05) and c\u2010erbB\u20102 expression (\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.05). On the other hand, increased TIMP\u20101 mRNA expression within the tumours showed a statistically significant correlation with ER detection (\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.01). Multivariate analysis revealed worse survival for patients with high TIMP\u20101 mRNA expression in the marginal portion of the tumours; the subgroup of these patients co\u2010expressing high levels of TIMP\u20101 mRNA within the tumours as well had even worse survival (\n                    <jats:italic>p<\/jats:italic>\n                    =0.042). In conclusion, our data support the multifunctional role of TIMP\u20101, particularly its growth\u2010promoting 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\u20101 with tumour cell differentiation is suggested by its topographical correlation with ER detection. Copyright \u00a9 2002 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.1129","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T08:29:56Z","timestamp":1033892996000},"page":"307-313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Enhanced mRNA expression of tissue inhibitor of metalloproteinase\u20101 (TIMP\u20101) in breast carcinomas is correlated with adverse 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