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Expression of Autocrine Motility Factor (AMF) and Its Receptor, AMFR, in Human Breast Cancer

Wen G. Jiang, Avraham Raz, Anthony Douglas-Jones and Robert E. Mansel

Metastasis and Angiogenesis Research Group, Wales College of Medicine, Cardiff University, Cardiff, UK (WGJ,AD-J,REM), and Karmanos Cancer Institute, Wayne State University, Detroit, Michigan (AR)

Correspondence to: Wen G. Jiang, Metastasis and Angiogenesis Research Group, University Department of Surgery, Wales College of Medicine, Cardiff University, Cardiff CF14 4XN, UK. E-mail: jiangw{at}cf.ac.uk

Autocrine motility factor (AMF) stimulates, via an autocrine route, the motility of cancer cells. The current study investigated the expression of AMF and its receptor, AMFR (gp78), in breast cancer and attempted to dissect a clinical link. Breast tumor tissues (n=120) and non-neoplastic normal tissues (n=32) were studied. AMF and AMFR distribution in tissues were assessed using immunohistochemistry and their transcripts were analyzed using RT-PCR and quantitative PCR. Median follow-up of the cohort was 10 years. Normal mammary epithelial cells, but not stromal and endothelial cells, weakly stained for AMF and AMFR. However, cancer cells showed stronger staining. Both AMF and AMFR transcripts were significantly higher in tumor than in normal tissues (p=0.003 and p=0.0001, respectively). High levels of AMF and AMFR were seen in patients who died of breast cancer (p=0.049, p=0.0435) and high AMF was also seen in patients who had local recurrence (p=0.039) compared with those who remained disease free. A significant correlation was seen between long-term survival and the AMFR:CK19 ratio, in which patients with high AMFR:CK19 ratio tumors had a significantly shorter survival (101.0 months, 80.6–121.4) compared with those with low ratio (136.0 months, 123.7–148.2), p=0.0331. In conclusion, AMF and AMFR are overexpressed in human breast cancer and are negatively associated with patients' clinical outcome. This strongly indicates that the AMF–AMFR complex plays an important role in the progression of breast cancer, as well as having a prognostic role. (J Histochem Cytochem 54:231–241, 2006)

Key Words: autocrine motility factor • AMF receptor • breast cancer • metastasis • prognosis • survival

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