title: Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer.
abstract: Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor.
authors.affiliation: Laboratory of Anatomy and Cellular Biology, Faculty of Medicine and Pharmacy, University of Mons, B-7000 Mons, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.affiliation: Laboratory of Anatomy and Cellular Biology, Faculty of Medicine and Pharmacy, University of Mons, B-7000 Mons, Belgium.
authors.forename: Nadège
authors.initials: N
authors.lastname: Kindt
authors.affiliation: Laboratory of Image, Signal Processing and Acoustics, Ecole Polytechnique de Bruxelles, B-1050 Brussels, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Decaestecker
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig Maximilians University, D-80539 Munich, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.affiliation: Laboratory of Histology, Faculty of Medicine and Pharmacy, University of Mons, B-7000 Mons, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
authors.affiliation: Department of Pathology, Erasme Hospital, B-1070 Brussels, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Noël
authors.affiliation: Laboratory of Anatomy and Cellular Biology, Faculty of Medicine and Pharmacy, University of Mons, B-7000 Mons, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Saussez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001940:Breast / Q000166:cytology* / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; C045084:invariant chain; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human