Atypical Tumor-stromal Fibroblasts in Invasive Ductal Carcinoma of the Breast

Abstract

Tumor-stromal fibroblasts have recently been reported to play important roles in the tumor progression of cancer in various organs. The purpose of this study was to investigate whether any characteristic histologic features of tumor-stromal fibroblasts could accurately predict the outcome of 1042 patients with invasive ductal carcinoma of the breast. We observed a small number of tumor-stromal fibroblasts with characteristic nuclear features existing inside and outside of fibrotic foci and named them atypical tumor-stromal fibroblasts. We then classified invasive ductal carcinomas into 4 types (1, 2, 3, and 4) according to the absence or presence of fibrotic foci and the absence or presence of atypical tumor-stromal fibroblasts. We then analyzed the outcome predictive powers of these types of invasive ductal carcinomas using multivariate analyses that included well-known clinicopathologic factors. The multivariate analyses showed that type 4 invasive ductal carcinomas with fibrotic foci and atypical tumor-stromal fibroblasts had significantly higher hazard ratios for tumor recurrence and tumor-related death, independent of the nodal status and histologic grade, and the type 2 invasive ductal carcinomas without fibrotic foci but with atypical tumor-stromal fibroblasts had a significant higher hazard ratio for tumor recurrence among patients with invasive ductal carcinoma with nodal metastasis and those with histologic grade 3 disease. The results of this study clearly indicated that the presence of atypical tumor-stromal fibroblasts, especially in fibrotic foci, is significantly associated with tumor recurrence and tumor-related death of patients with invasive ductal carcinoma of the breast.