Breast Cancer Expression of DAP12 is Associated With Skeletal and Liver Metastases and Poor Survival

Macrophages are an important cellular factor in breast cancer (BRC) progression and metastasis. DNAX activating protein of 12 kD (DAP12) is essential factor for macrophage fusion function. This study was conducted to investigate the expression and significance of DAP12 expression in BRC. DAP12 is expressed in BRC cells and associated with poor survival, liver metastases, and bone metastases. These data provide new insight into the pathophysiology of macrophages in BRC. Background: The transmembrane adapter protein, DAP12, transduces activation signals for several arrays of receptors, including human signal-regulatory protein, DAP12-associating lectin-1, triggering receptor expressed on myeloid cells-1, -2, and -3, in natural killer cells, granulocytes, monocytes/macrophages, and dendritic cells. The macrophage-specific antigen, Cluster of Differentiation 163 (CD163), is expressed in breast and colorectal cancers and is associated with early cancer recurrence and poor prognosis. It was recently shown that fusion between intestinal tumor cells and macrophages results in nuclear reprogramming with hybrid transcripts from both cells of origin. The role of DAP12 in the fusion process is not known. This study investigates the expression of DAP12 in BRC cells, and its relation to other macrophage traits and to the clinical progression of disease. Materials and Methods: Immunostaining of DAP12 and CD163 was performed and evaluated in paraffin-embedded specimens from 132 patients with BRC. The outcomes were analyzed in relation to clinicopathological data. Results: DAP12 expression in cancer cells was positive in 66 percent of the cancers and was associated with high tumor grade (P = .015), and with liver (P = .047) and skeletal (P = .067), but not with lung metastases (P = 1.00). Patients with BRC expressing DAP12 had poor prognosis, with higher recurrence rates of skeletal (P = .018) and liver metastases (P = .047), and shorter survival time (P = .0060). Conclusion: We suggest that macrophage traits in BRC cells facilitate the metastatic process and that DAP12 expression might promote metastatic homing to bone and liver tissues. (C) 2013 Elsevier Inc. All rights reserved.