Abstract 694: Characterization of a novel monoclonal antibody to Glia maturation factor-beta showing significant clinical utility in the identification of breast carcinoma

Abstract

Abstract Background: Glia maturation factor beta (GMF-beta) is a growth and differentiation factor of brain cells, stimulation of neural degeneration and inhibition of proliferation of tumor cells. It was recently found to involve in the progression of serous ovarian carcinoma. In the present study, we generated a novel antibody against human GMF-beta and investigated the potential of GMF-beta as a biomarker in breast cancer. Methods and findings: We generated a novel monoclonal antibody (mAb), AB-GMF-beta using hybridoma technology and native protein as an immunogen. This mAb is of IgG1 (kappa) type. It specifically recognized both native and denatured human GMF-beta protein and displayed high affinity as assessed by ELISA, immunohistochemistry assay, western blot and flow cytometry applications. Using this mAb in competitive ELISA, we showed for the first time that soluble GMF-beta level is significantly increased in metastatic breast cancer patients’ plasma which directly correlated with GMF-beta expression pattern in metastatic breast cancer tissues. Tissue expression of GMF-beta was determined by using immunohistochemical techniques. Seventy normal and 241 breast cancer tissues were included which consist of 194 ductal and 47 lobular carcinoma samples. Most of normal tissues showed negative or weak nuclear staining, while different levels of nuclear, and diffuse and weak cytoplasmic staining were observed in cancer sections. To evaluate the immunoreactivity of GMF-beta associated with tumor histological types, the staining intensity in nucleus were scored as 0, 1+, 2+ and 3+. Grade 0 and 1+ were defined as negative and 2+ and 3+ as positive. Forty four percent of ductal carcinomas showed strong staining whereas it is significantly increased to 72.3% in lobular tumors (p<0.001). Conclusion: The novel AB-GMF-beta mAb showed high performance in blood and tissue assays. The circulating GMF-beta levels and expressions in breast tissues are significantly increased in breast cancer patients in comparison of normal controls. The increased tissue expressions in breast carcinoma associate with histological tumor types. Our data suggest the potential clinical use of GMF-beta as a biomarker for diagnosis and prognosis in blood and tissue as well as a therapeutic target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 694. doi:1538-7445.AM2012-694