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Analyses for the biological characteristics of tumor cells and tumor stromal cells in vessels and lymph nodes that determine the ability of metastasis and invasion of cancers.

分析血管和淋巴结中肿瘤细胞和肿瘤基质细胞的生物学特性，决定癌症的转移和侵袭能力。

基本信息

批准号：
15590329
负责人：
HASEBE Takahiro
金额：
$ 2.11万
依托单位：
National Cancer Center Research Institute East
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590329/
关键词：
Breast cancer Invasive ductal carcinoma Colorectal cancer Fibroblast Endothelial cell Fibrotic focus Metastasis Invasion

项目摘要

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 … More 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

通过回顾分析，证实乳腺浸润性导管癌(IDCs)成纤维细胞增殖活性对预后的意义。此外，我们前瞻性地调查了439名IDC患者中FF的预后意义，并通过多因素分析清楚地证明IDC中FF的存在是IDC患者预后的一个非常重要的独立组织学预测因素。尤其是直径大于8 mm的IDC患者，根据其淋巴结状态或激素受体状态进行多因素分析，肿瘤复发和远处转移的危险性(HR)显著增加。结直肠癌的中心凹陷区(CDA)厚度(肿瘤厚度)是判断结直肠癌患者预后的重要指标。我们研究了肿瘤和间质成分的增殖活性是否在肿瘤厚度增加…中起重要作用。157T3型溃疡型结直肠癌更易发生和进展。根据肿瘤厚度将结直肠癌分为薄型和厚型两组。肿瘤间质成纤维细胞的增殖活性是唯一与肿瘤厚度显著相关的参数。在多因素分析中，肿瘤间质成纤维细胞的高增殖活性与肿瘤复发显著相关，而肿瘤间质内皮细胞的高增殖活性是肿瘤复发的重要参数。乳腺IDCs由间质浸润性肿瘤、淋巴管肿瘤和结节内肿瘤组成。我们在393名IDC患者中调查了血管和结节肿瘤的组织学特征是否与增加的淋巴结转移和预后显著相关。多因素分析显示，在无淋巴结转移的IDC中，FF的大小、淋巴管癌栓中的&gt；6凋亡图形和距肿瘤边缘&gt；3 mm的肿瘤栓子显著增加了肿瘤复发的比率。在有结节转移的IDC中，血管肿瘤、有丝分裂的结节肿瘤、严重间质和链状生长的肿瘤以及有结外侵犯的IDC中的凋亡图形&gt；2显著增加了肿瘤复发或死亡的比率。根据IDC的组织学特征，提出了一种新的预后组织学分类--原发肿瘤-血管肿瘤-结节肿瘤(PVN)。采用COX比例风险回归模型进行多因素分析，比较PVN分类对393例IDC患者肿瘤复发和死亡的预测能力，这些分类基于以下组织学分类：1)pTNM分类，2)Nottingham预后指数，3)改良Nottingham预后指数，4)组织学分级。在无淋巴结转移的IDC中，只有PVN分类显著增加了肿瘤复发和死亡的风险(HR)，而与激素受体状态无关。同样，在有淋巴结转移的IDC中，只有PVN分类显著增加了肿瘤复发和死亡的比率，而与激素受体状态无关。我们的结论是PVN预后组织学分型是乳房IDC的最佳分类。上述研究首次证明，血管和淋巴结中的肿瘤间质细胞以及原发侵袭性肿瘤在乳腺癌和结直肠癌的肿瘤进展中起着重要作用。较少