Differential Expression of Milk Fat Globule-EGF Factor 8 (MFG-E8) in Breast Cancers
Yanan Fang, Qiang Xie, Huiyun Wang, Chuanwei Yang, Albert S Braverman, Constantine A Axiotis. SUNY Downstate Medical Center/Kings County Hospital, Brooklyn, NY; BIDMC, Boston, MA; MGH, Boston, MA; SUNY Downstate Medical Canter/Kings County Hospital, Brooklyn, NY
Background: Levels of milk fat globule-EGF factor 8 (MFG-E8) mRNA, determined by microarray and in situ hybridization, are high in triple negative (ER/progesterone receptor/HER2/neu negative) breast cancer, but lower in estrogen receptor positive (ER+) breast tumors. Approximately 26% women who have breast cancer have p53 mutations. p53 mutation is most commonly associated with ER-/PR- tumors in premenopausal women. The patient with p53 mutations usually have poorer prognosis. Immunohistochemistry has been used to determine MFG-8 levels and its correlation with ER expression in breast biopsies, but their correlation with p53 and HER2/neu expression is not known.
Design: Benign breast lesions, and ER, HER2/neu and p53 positive and negative breast cancers were stained with an anti-MFG-E8 antibody.
Results: MFG-E8 was absent in 5 benign breast lesions (1 fibroadenoma, 2 intraductal papilloma, and 2 sclerosing adenosis). MFG-E8 was present in the plasma membrane and cytoplasm of 18 of 26 (69%) triple negative tumors. The presence of p53 mutations was known in all 26 triple negative tumors; 5 of the 9 tumors (56%) without p53 mutations, and 13 of 17 tumors (77%) with mutations were positive for MFG-E8. 3 out of 7 ER-, Her2/neu+ (43%) tumors showed positive staining for MFG-E8. Seven ER/HER2+ tumors and 7 ER+, HER2- tumors were negative for MFG-E8.
Conclusions: Immunohistochemical staining confirms the results of gene expression analysis of breast tumors for MFG-E8 mRNA. The protein product is absent in benign breast lesions and in ER+ tumors, whether HER2/neu+ or HER2/neu-, but present in most ER- tumors. MFG-E8 is expressed highest in triple negative, p53+ tumors. MFG-E8 protein may prove to be an independent marker for the latter tumors, and have implications for their histogenesis.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 30, Wednesday Morning