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Am J Pathol. 2000 May;156(5):1701-10.

Proliferative activity of intratumoral fibroblasts is closely correlated with lymph node and distant organ metastases of invasive ductal carcinoma of the breast.

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Pathology Division, the National Cancer Center Research Institute East, Kashiwa, Chiba, Japan.


Mitotic figures of fibroblasts are seen within invasive ductal carcinoma (IDC) of the breast. This suggests that the proliferative activity of fibroblasts may play an important role in IDC tumor progression. The purpose of this study was to examine whether the proliferative activity of fibroblasts can predict lymph node metastasis (LNM) or distant-organ metastasis (DOM) of IDCs. Two hundred four consecutive patients with IDC of the breast surgically treated at the National Cancer Center Hospital East constituted the basis of this study. Proliferative activity of fibroblasts was immunohistochemically evaluated by the mouse MIB-1 monoclonal antibody against Ki-67 antigen. The MIB-1 labeling index was the percentage of fibroblasts with positively stained nuclei, and fields for cell counting were selected in inner and outer areas within IDCs. In both areas, 300 fibroblasts were counted in each high-power field. The significance of proliferative activity of fibroblasts on LNM or DOM was compared with well-known prognostic parameters. Multivariate analyses demonstrated that a MIB-1 labeling index of more than 10% of fibroblasts in the inner area of IDCs significantly increased the relative risk of LNM and hazard rate of DOM (P < 0.001 and P = 0.007, respectively). The present study indicated that the metastatic ability of IDCs is closely dependent on proliferative activity of fibroblasts in the inner area.

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