A novel multipurpose monoclonal antibody for evaluating human c-Met expression in preclinical and clinical settings.

Abstract

The inappropriate expression of the c-MET cell surface receptor in many human solid tumors necessitates the development of companion diagnostics to identify those patients who could benefit from c-MET targeted therapies. Tumor tissues are formalin fixed and paraffin embedded (FFPE) for histopathologic evaluation, making the development of an antibody against c-MET that accurately and reproducibly detects the protein in FFPE samples an urgent need. We have developed a monoclonal antibody (mAb), designated MET4, from a panel of MET-avid mAbs, based on its specific staining pattern in FFPE preparations. The accuracy of MET4 immunohistochemistry (MET4-IHC) was assessed by comparing MET4-IHC in FFPE cell pellets with immunoblotting analysis. The technical reproducibility of MET4-IHC possessed a percentage coefficient of variability of 6.25% in intra-assay and interassay testing. Comparison with other commercial c-MET antibody detection reagents demonstrated equal specificity and increased sensitivity for c-MET detection in prostate tissues. In cohorts of ovarian cancers and gliomas, MET4 reacted with ovarian cancers of all histologic subtypes (strong staining in 25%) and with 63% of gliomas. In addition, MET4 bound c-MET on the surfaces of cultured human cancer cells and tumor xenografts. In summary, the MET4 mAb accurately and reproducibly measures c-MET expression by IHC in FFPE tissues and can be used for molecular imaging in vivo. These properties encourage further development of MET4 as a multipurpose molecular diagnostics reagent to help to guide appropriate selection of patients being considered for treatment with c-MET-antagonistic drugs.

DOI: 10.1097/PAI.0b013e3181816ae2
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@article{Knudsen2009ANM, title={A novel multipurpose monoclonal antibody for evaluating human c-Met expression in preclinical and clinical settings.}, author={Beatrice S Knudsen and Ping Zhao and James Resau and Sandra Cottingham and Ermanno Gherardi and Eric Xu and Bree Berghuis and Jennifer Daugherty and Tessa Grabinski and Jose Toro and Troy Giambernardi and R Scot Skinner and Milton Gross and Eric Hudson and Eric Kort and Ernst Lengyel and Aviva Ventura and Richard A West and Qian Xie and Rick Hay and George Vande Woude and Brian Cao}, journal={Applied immunohistochemistry & molecular morphology : AIMM}, year={2009}, volume={17 1}, pages={57-67} }