[Relationship between tissue inhibitors of metalloproteinase and metastasis and prognosis in breast cancer].
OBJECTIVE
To investigate the clinical significance of tissue inhibitors of metalloproteinase (TIMP) -3 and TIMP-4 in human breast cancer.


METHODS
The levels of TIMP-3 and TIMP-4 mRNA in paraffin-embedded breast carcinoma specimens from 70 patients with primary invasive breast cancer who had undergone radical mastectomy from January of 1984 to December of 1985 were assessed by in situ hybridization assay. Intratumoral microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression were detected by the standard streptavidin biotin peroxides method.


RESULTS
Both TIMP-3 and TIMP-4 mRNA expressions were higher in patients with axillary lymph node metastasis than in those without metastasis (P < 0.01), and patients with higher expression of any of these two genes had a better prognosis than those with lower expression (P < 0.01). We introduced lymph node status, TNM staging, MVD and VEGF expression, plus TIMP-3 and TIMP-4 to the Cox's proportional hazards regression model for significant analysis, and found that the TIMP-3, TNM staging and MVD play an important role in prognosis of this group.


CONCLUSIONS
TIMP-3 and TIMP-4 are correlated with metastasis in breast cancer, and TIMP-3 demonstrates an independent prognostic factor for the patients. These results provide a valuable clue for developing new, practical prognosticators in breast cancer patients.
Jiang
X
X
Department of Surgery, College of Clinical Oncology, Beijing Medical University, China.
Huang
X
X
Li
J
J
Shi
Y
Y
Zhou
L
L
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D017403:In Situ Hybridization / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000097792:Tissue Inhibitor of Metalloproteinase-4
D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D042461:Vascular Endothelial Growth Factor A; D000097792:Tissue Inhibitor of Metalloproteinase-4; C088390:TIMP3 protein, human; C467484:VEGFA protein, human