Expression of interleukin-1 beta in human breast carcinoma

BACKGROUND. Interleukin 1 beta (IL-1 beta) is a multifunctional cytokine that up-regulates the inflammatory response. It is not known whether IL-IP plays a major role in human malignancy. To determine whether IL-1 beta might be involved in breast carcinoma progression, the authors measured the IL-1 beta content in tissue extracts from >200 invasive breast carcinomas and smaller numbers of ductaI carcinoma in situ (DCIS) and benign lesions. METHODS. IL-1 beta content was measured by an enzyme-linked immunoadsorbent assay and analyzed to determine whether these values were correlated with the contents of scatter factor (SF) (an invasogenic and angiogenic cytokine, von Willebrand's factor (VWF) (a marker of endothelium), thrombospondin-l (TSP1) (an antiadhesive and antiangiogenic glycoprotein, and tumor necrosis factor-alpha (TNF alpha) (another proinflammatory cytokine). Studies were also performed to determine whether IL-1 beta content was correlated with other pathologic and immunochemical variables that have been utilized or proposed as prognostic indicators for breast carcinoma. RESULTS. The most important findings of these studies were: 1) immunoreactive IL-1 beta was detected in approximately 90% of invasive breast carcinomas; 2) IL-IP levels were significantly higher in invasive carcinomas than in a group of DCIS and benign lesions; 3) high IL-1 beta content in invasive carcinomas was significantly associated with higher contents of SF, VWF, and TSP1, but not TNF alpha; and 4) there was a trend toward higher IL-1 beta content in invasive carcinomas with a group of other parameters that suggest a biologically more aggressive tumor (estrogen receptor negativity, high tumor grade, p53 positivity, and bcl-2 negativity); and the proportion of invasive tumors with these characteristics was significantly increased in a subgroup of tumors having very high IL-1 beta content. The authors also found a correlation between high IL-1 beta content and CD68 positivity, suggesting that macrophages may account for some of the IL-1 beta present in human breast carcinoma tissue. CONCLUSIONS. These findings suggest that significant titers of IL-1 beta are present within the microenvironment of most breast carcinomas and that a high IL-1 beta content is often associated with tumor invasiveness and with other pathologic features suggestive of an aggressive tumor biology. (C) 1997 American Cancer Society.