Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence

Yale University, New Haven, Connecticut, United States
Clinical Cancer Research (Impact Factor: 8.72). 09/1998; 4(8):1851-6.
Source: PubMed


The macrophage colony-stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, regulates normal proliferation and differentiation of macrophages and trophoblasts. Recent research found abnormal expression of CSF-1R in human carcinomas of the breast, endometrium, and ovary. Furthermore, activation of CSF-1R by its ligand has been shown to regulate invasiveness and anchorage-independent growth in breast carcinoma cells. To study the significance of CSF-1R expression in breast cancer, we designed a case-controlled immunohistochemical study. We chose 80 patients from a database of 1200 early stage I or II breast cancer patients treated with conservative surgery and radiation therapy. Expression of CSF-1R in the tumors of 40 patients who experienced an ipsilateral breast tumor recurrence (IBTR) as a primary site of relapse were compared with 40 patients who had not experienced an IBTR. The index and control patients were matched by age, clinical stage, nodal status, and follow-up. Paraffin-embedded sections were immunostained with antibodies directed toward CSF-1R. For the CSF-1R antibody, a total of 28 index cases (70%) demonstrated strong staining, whereas only 16 control cases (40%) demonstrated high immunoreactivity (P = 0.007). The CSF-1R antibody showed a positive correlation for local relapse, but no correlation was found between CSF-1R expression and distant metastasis. In summary, our findings provide evidence for the poor prognostic role of CSF-1R in IBTR.

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Available from: Andrew A Gumbs, Jun 29, 2015
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    • "The proto-oncogene c-fms encodes the only known receptor (CSF-1R) for CSF-1 (Sherr and others 1985; Dai and others 2002). The expression of CSF-1 and its receptor in neoplastic epithelial breast cancer cells correlates well with a poor prognosis and is predictive of ipsilateral recurrence (Scholl and others 1994; Maher and others 1998; Kluger and others 2004). CSF-1 promotes metastasis, stimulates angiogenesis, and participates in a paracrine loop with EGF to spur tumor cell invasion in mouse models (Lin and others 2001; Aharinejad and others 2002; Aharinejad and others 2004; Wyckoff and others 2004). "
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    • "Both CSF1 and its receptor CSF1R also play roles in trophoblast survival and reproductive development (for review see [33]). Additionally, in some cancers, such as breast, ovarian and endometrial cancer, these proteins are overexpressed, and their expression can be a marker for poor prognosis [30], [32], [39], [40]. In human breast cancer, the levels of CSF1R correlate with local relapse after radiation therapy, but do not correlate with metastasis; these data were the first to suggest that high levels of CSF1R might promote radio-resistance [39]. "
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    • "paracrine activation). Consistent with this, in breast cancer patients, the expression of both CSF-1 and its receptor in neoplastic epithelial cells strongly correlates with poor prognosis and is predictive of ipsilateral recurrence [18]–[20]. In addition, the presence of tumor associated macrophages in breast tumors also correlates with poor prognosis [19], [21] and, in mouse models, CSF-1 promotes metastasis [22], stimulates angiogenesis [23], [24] and is involved in a paracrine loop with EGF to promote tumor cell invasion [25]. "
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