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The purpose of this study was to determine whether p53 protein expression in tumor stromal fibroblasts assessed immunohistochemically by the Allred score system is significantly associated with nodal metastasis by invasive ductal carcinoma (IDC), and significantly associated with the outcome of 1042 IDC patients according to adjuvant therapy status, UICC pTNM stage, and triplenegative IDC status, in multivariate analyses with well-known clinicopathological factors. The Allred scores for p53 expression in tumor stromal fibroblasts were significantly associated with the number of nodal metastases, and Allred scores of 4-8 for p53 in tumor stromal fibroblasts significantly increased the hazard rate for distant organ metastasis or for tumor death in the triple-negative IDC patients, and the UICC pTNM stage I, II, and III patients. The results indicated that p53 protein expression in tumor stromal fibroblasts is closely associated with the number of nodal metastases and the outcome of IDC patients. (Cancer Sci 2009; 100: 2101-2108 I t has recently been reported that the gene expression and protein expression profiles of the tumor stroma play very important roles in tumor progression in carcinoma, (1)(2)(3) and the interaction between tumor and stromal cells also plays a very important role in tumor progression by carcinoma.(4-6) We and others have already reported that a characteristic histological feature of tumor stroma, a fibrotic focus, is a very useful prognostic histological tumor stromal indicator for accurately predicting the outcome of patients with invasive ductal carcinoma (IDC), (7)(8)(9)(10) and that growth factors produced by tumor cells and tumor stromal cells play a very important role in tumor progression by IDC.(11) In addition, proliferative activity of tumor stromal fibroblasts plays a very important role in nodal metastasis and distant organ metastasis by IDC.(12,13) These findings strongly suggest a significant role of the tumor stroma in tumor progression by IDC.p53 is the most commonly mutated gene in human neoplasms, (14) and the p53 tumor suppressor protein is involved in the cell cycle, checkpoint control, repair of DNA damage, and apoptosis.(15,16) Also, besides their well-studied cell-autonomous role in cancer cells, mutations of the p53 tumor suppressor gene have been described in stromal fibroblasts of breast and prostate carcinoma in humans and experimental animals. (17)(18)(19)(20) A high frequency of p53 mutations in tumor cells and the surrounding stroma has also reported, (17) and p53 mutations in breast cancer stromal cells have been reported to be closely associated with nodal metastasis.(21) Based on the above findings, the p53 status of tumor stromal fibroblasts may play a very important role in carcinoma progression by IDC.The purpose of the present study was to determine whether p53 protein expression in tumor stromal fibroblasts is significantly associated with nodal metastasis by IDC, and significantly associated with the outcome of IDC patients with and without adjuvant th...

The present study investigated fibrotic foci (FFs), the grading system for lymph vessel tumor emboli (LVTEs), and the histological characteristics of nodal metastatic tumors that were significantly associated with the outcomes of 115 patients with invasive ductal carcinoma (IDC) who had received neoadjuvant chemotherapy. We compared the outcome predictive power of FFs, the grading system for LVTEs, and the histological characteristics of metastatic tumors in lymph nodes with the well-known clinicopathological characteristics of tumor recurrence and tumor-related death in multivariate analyses. The presence of FFs, as assessed by a biopsy performed before neoadjuvant chemotherapy, significantly increased the hazard rates (HRs) for tumor-related death in all the cases and in cases with nodal metastasis. The grading system for LVTEs, which was assessed using surgical specimens obtained after neoadjuvant chemotherapy, was significantly associated with increasing hazard rates (HRs) for tumor recurrence and tumor-related death in all the cases and in cases with nodal metastasis. Moderate to severe stroma in nodal metastatic tumors and five or more mitotic figures in nodal metastatic tumors were significantly associated with elevated HRs for tumor recurrence and tumor-related death among all the cases. These results indicated that FFs, the grading system for LVTEs, and the histological characteristics of tumor cells in lymph nodes play important roles in predicting the tumor progression of IDCs of the breast in patients treated with neoadjuvant