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The Korean Journal of Pathology 2000;34(9): 652-664.
Expression of Matrix Metalloproteinase and Tissue Inhibitor of Metallproteinase in Breast Carcinoma Related to Angiogenesis and Invasion.
Yoon Jung Choi, Woo Hee Jung, Hy De Lee, Kwang Gil Lee
1Department of Diagnostic Pathology, Pundang Jesaeng General Hospital, Sungnam 463-050, Korea.
2Departments of Pathology, Yonsei University College of Medicine.
3Departments of General Surgy, Yonsei University College of Medicine.
4Department of Pathology, Wonju Medical College, Yonsei University.
ABSTRACT
Among the enzymes which are responsible for basement membrane breakdown, matrix metalloproteinases (MMP) form a family of neutral proteases that are regulated at the levels of gene transcription, proenzyme activation by the cleavage of protein, and the inhibition of the active enzyme by tissue inhibitors of matrix metalloproteinases (TIMP). Recent reports have demonstrated that the expression of these proteolytic enzymes are elevated in several solid tumors and that it can be associated with invasiveness and poor prognosis. We examined the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 by immunohistochemistry in 160 cases of infiltrating ductal carcinoma. And we compared these data with the established prognostic parameters - tumor size, nodal status, clinical stage, hormonal receptor status, microvessel density, and TGF-beta1 expression in order to evaluate how MMP and TIMP expression are associated with breast cancer progression and prognosis. Microvessel density in invasive breast carcinoma was significantly correlated with tumor size and recurrence (p<0.05). The immunohistochemical expression of TGF-beta1 was significantly associated with tumor size, lymph node metastasis, and clinical stage (p<0.05). The microvessel density was significantly correlated with TGF-beta1 expression in more than 50% of tumor cells. The immunohistochemical expression of MMP-2 and MMP-9 were significantly correlated with nodal metastasis and absence of immunoreactivity for estrogen and progesterone receptors. The immunohistochemical expression of TIMP-1 was inversely correlated with clinical stage and microvessel density while that of TIMP-2 was inversely correlated with clinical stage (p<0.05). Small size of tumor, presence of progesterone receptor, highly differentiated histologic grade, and absence of immunoreactivity for MMP-9 were significantly associated with higher survival rate, but in multivariate analysis only tumor size and MMP-9 expression appeared to affect survival independently.
Key Words: Infiltrating ductal carcinoma; MMP; TIMP; Microvessel density; Survival rate