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.
Department of Pathology, Athens National University Medical School, Greece. lnakopou@cc.uoa.gr
Lydia
L
Nakopoulou
Ioanna
I
Giannopoulou
Kalliopi
K
Stefanaki
Effie
E
Panayotopoulou
Ioanna
I
Tsirmpa
Paraskevi
P
Alexandrou
John
J
Mavrommatis
Sophia
S
Katsarou
Panagiotis
P
Davaris
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000401:mortality; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012259:Ribonuclease, Pancreatic; D015996:Survival Rate; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*
D015415:Biomarkers; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D012259:Ribonuclease, Pancreatic; D019715:Tissue Inhibitor of Metalloproteinase-1