Interleukin 1 system and sex steroid receptor expression in human breast cancer: interleukin 1alpha protein secretion is correlated with malignant phenotype.

The interleukin 1 (IL-1) system plays an important role in human pathology and is involved in the local control of malignant disease. However, little is known about its expression in breast cancer and its correlation with prognostic parameters such as receptor status and grading. The expression of IL-1alpha and other IL-1 family members was analyzed by reverse transcription-PCR, ELISA, and immunohistochemistry in breast cancer cell lines, tumor-derived fibroblasts, and breast cancer tissue biopsies and compared with sex steroid receptor status and grading. In breast cancer cell lines, IL-1alpha and -beta gene expression was present in the phenotypically most malignant cell lines, whereas estrogen receptor (ER) alpha and progesterone receptor mRNA expression was confined to lines that exhibit a rather benign phenotype. Only the highly malignant receptor-negative tumor cell line MDA MB 231 expressed IL-1alpha protein, and none of the cell lines secreted IL-1beta. Biopsies from breast cancer tissue expressed various amounts of IL-1alpha, IL-1beta, and IL-1 receptor antagonist mRNA, but consistently high levels of IL-1tIR. IL-1alpha protein expression was detected in tumor cells and/or adjacent stroma in 88%, and epithelial protein expression was correlated with both poor differentiation (P = 0.002; r = 0.469) and decreasing epithelial ERalpha expression (P = 0.004; r = -0.387). Furthermore, stromal IL-1alpha was predominant in areas with low or absent ERalpha protein expression in neighboring tumor epithelium (P = 0.001; r = -0.457). We have demonstrated the presence of a functional IL-1 system in breast cancer and found that IL-1alpha is inversely correlated with local sex steroid receptor expression. We hypothesize that the unphysiological expression of IL-1alpha in less differentiated and ERalpha-negative tumors might contribute to their local invasiveness and malignant behavior.