| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Prognostic significance of proliferative activity of fibroblasts consisting of a fibrotic focus(FF) in invasive ductal carcinomas(IDCs) of the breast was confirmed by the retrospective analysis. In addition, we prospectively investigated the prognostic significance of a FF in 439 IDC patients, and clearly demonstrated that the presence of a FF in IDCs is a very important independent prognostic histological predictor of the outcome of IDC patients by multivariate analyses. Especially, IDC patients with a FF of greater than 8 mm in diameter significantly increased the hazard rates(HRs) of tumor recurrence and distant-organ metastasis in multivariate analyses according to their nodal status or hormone receptor status.
The central depressed area(CDA) thickness (tumor thickness) of colorectal cancers is an important prognostic parameter for colorectal cancer patients. We examined whether the proliferative activities of tumor and stromal components play important roles in tumor thickness incr
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ease and the progression of 157 T3 ulcerative-type colorectal cancers. Colorectal cancers were classified into thin and thick groups according to tumor thickness. The tumor-stromal fibroblast proliferative activity was the only parameter significantly associated with tumor thickness. High tumor-stromal fibroblast proliferative activity showed significant correlations with tumor recurrence in the thin group, and high proliferative activity of tumor-stromal endothelial cells was a significant parameter of tumor recurrence in the thick group in multivariate analyses.
IDCs of the breast are composed of stroma-invasive tumors, tumors in lymph vessels and in nodes. We investigated whether the histological characteristics of tumors in vessels and nodes are significantly associated with increased nodal metastases as well as outcomes, in 393 IDC patients. Multivariate analyses showed that, in IDCs without nodal metastasis, FF dimension, and lymph vessel tumor emboli with >6 apoptotic figures and those with a distance from the tumor margin >3 mm had significantly increased the HRs of tumor recurrence. In IDCs with nodal metastases, apoptotic figures >2 in blood vessel tumors, nodal tumors with mitotic figures >5,those with severe stroma and strand growth, and >5 nodes with extra-nodal invasion significantly increased the HRs of tumor recurrence or death.
A new prognostic histological classification, the Primary tumor-Vessel tumor-Nodal tumor(PVN) classification, was devised based on the histological characteristics of IDCs with and without nodal metastasis. Multivariate analyses using the Cox proportional hazard regression models were used to compare the ability of the PVN classification to predict tumor recurrence and death in 393 IDC patients based on the following histological classifications : 1)the pTNM classification, 2)the Nottingham Prognostic Index, 3) the modified- Nottingham Prognostic Index, and 4)the histologic grade. In IDCs without nodal metastasis, only the PVN classification significantly increased the hazard rates(HR) of tumor recurrence and death independent of the hormone receptor status. Similarly, in IDCs with nodal metastases, only the PVN classification significantly increased the HRs of tumor recurrence and death independent of the hormone receptor status. We conclude that the PVN prognostic histological classification is the best classification available for IDC of the breast.
These above studies firstly demonstrate that tumor-stromal cells in vessels and lymph nodes as well as in primary-invasive tumors play important roles in tumor progression of breast and colorectal cancers in the world. Less
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